{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:13:44Z","timestamp":1790957624677,"version":"4.1.0"},"reference-count":196,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:00:00Z","timestamp":1674604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondation pour la Recherche Medicale","award":["FRM DPC20170139474"],"award-info":[{"award-number":["FRM DPC20170139474"]}]},{"name":"Fondation pour la Recherche Medicale","award":["n\u00b0PJA 20161204650"],"award-info":[{"award-number":["n\u00b0PJA 20161204650"]}]},{"name":"Fondation ARC pour la recherche sur le cancer\u201d","award":["FRM DPC20170139474"],"award-info":[{"award-number":["FRM DPC20170139474"]}]},{"name":"Fondation ARC pour la recherche sur le cancer\u201d","award":["n\u00b0PJA 20161204650"],"award-info":[{"award-number":["n\u00b0PJA 20161204650"]}]},{"name":"Gemluc","award":["FRM DPC20170139474"],"award-info":[{"award-number":["FRM DPC20170139474"]}]},{"name":"Gemluc","award":["n\u00b0PJA 20161204650"],"award-info":[{"award-number":["n\u00b0PJA 20161204650"]}]},{"name":"Plan Cancer INSERM","award":["FRM DPC20170139474"],"award-info":[{"award-number":["FRM DPC20170139474"]}]},{"name":"Plan Cancer INSERM","award":["n\u00b0PJA 20161204650"],"award-info":[{"award-number":["n\u00b0PJA 20161204650"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Peroxisome proliferator activated receptors, including PPAR\u03b1, PPAR\u03b2\/\u03b4, and PPAR\u03b3, are ligand-activated transcription factors belonging to the nuclear receptor superfamily. They play important roles in glucose and lipid metabolism and are also supposed to reduce inflammation and atherosclerosis. All PPARs are involved in angiogenesis, a process critically involved in cardiovascular pathology. Synthetic specific agonists exist for all PPARs. PPAR\u03b1 agonists (fibrates) are used to treat dyslipidemia by decreasing triglyceride and increasing high-density lipoprotein (HDL) levels. PPAR\u03b3 agonists (thiazolidinediones) are used to treat Type 2 diabetes mellitus by improving insulin sensitivity. PPAR\u03b1\/\u03b3 (dual) agonists are supposed to treat both pathological conditions at once. In contrast, PPAR\u03b2\/\u03b4 agonists are not in clinical use. Although activators of PPARs were initially considered to have favorable effects on the risk factors for cardiovascular disease, their cardiovascular safety is controversial. Here, we discuss the implications of PPARs in vascular biology regarding cardiac pathology and focus on the outcomes of clinical studies evaluating their benefits in cardiovascular diseases.<\/jats:p>","DOI":"10.3390\/ijms24032345","type":"journal-article","created":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T01:57:07Z","timestamp":1674698227000},"page":"2345","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Pharmacological Utility of PPAR Modulation for Angiogenesis in Cardiovascular Disease"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2746-0707","authenticated-orcid":false,"given":"Nicole","family":"Wagner","sequence":"first","affiliation":[{"name":"CNRS, INSERM, Universit\u00e9 C\u00f4te d\u2019Azur, iBV, 06107 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5483-7760","authenticated-orcid":false,"given":"Kay-Dietrich","family":"Wagner","sequence":"additional","affiliation":[{"name":"CNRS, INSERM, Universit\u00e9 C\u00f4te d\u2019Azur, iBV, 06107 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1038\/s41569-021-00569-6","article-title":"PPAR control of metabolism and cardiovascular functions","volume":"18","author":"Montaigne","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1517\/14656566.2014.876992","article-title":"New peroxisome proliferator-activated receptor agonists: Potential treatments for atherogenic dyslipidemia and non-alcoholic fatty liver disease","volume":"15","author":"Sahebkar","year":"2014","journal-title":"Expert. Opin. Pharmacother."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1177\/2045894018812053","article-title":"PPAR\u03b2\/\u03b4 a potential target in pulmonary hypertension blighted by cancer risk","volume":"9","author":"Mitchell","year":"2019","journal-title":"Pulm. Circ."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Khuchua, Z., Glukhov, A.I., Strauss, A.W., and Javadov, S. (2018). Elucidating the Beneficial Role of PPAR Agonists in Cardiac Diseases. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113464"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Wagner, K.D., and Wagner, N. (2020). PPARs and Myocardial Infarction. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249436"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.amjmed.2011.08.025","article-title":"The cardiovascular effects of peroxisome proliferator-activated receptor agonists","volume":"125","author":"Friedland","year":"2012","journal-title":"Am. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Cheng, H.S., Tan, W.R., Low, Z.S., Marvalim, C., Lee, J.Y.H., and Tan, N.S. (2019). Exploration and Development of PPAR Modulators in Health and Disease: An Update of Clinical Evidence. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20205055"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Wagner, N., and Wagner, K.D. (2020). PPARs and Angiogenesis-Implications in Pathology. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165723"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"17042","DOI":"10.1074\/jbc.274.24.17042","article-title":"Endothelial cell apoptosis induced by the peroxisome proliferator-activated receptor (PPAR) ligand 15-deoxy-Delta12, 14-prostaglandin J2","volume":"274","author":"Hla","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1161\/01.CIR.0000048892.83521.58","article-title":"Arterial and cardiac aging: Major shareholders in cardiovascular disease enterprises: Part I: Aging arteries: A \u201cset up\u201d for vascular disease","volume":"107","author":"Lakatta","year":"2003","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1161\/01.CIR.0000048893.62841.F7","article-title":"Arterial and cardiac aging: Major shareholders in cardiovascular disease enterprises: Part II: The aging heart in health: Links to heart disease","volume":"107","author":"Lakatta","year":"2003","journal-title":"Circulation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1038\/ncpcardio1324","article-title":"Vascular aging: Insights from studies on cellular senescence, stem cell aging, and progeroid syndromes","volume":"5","author":"Minamino","year":"2008","journal-title":"Nat. Clin. Pract. Cardiovasc. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e105242","DOI":"10.15252\/embj.2020105242","article-title":"Decreased blood vessel density and endothelial cell subset dynamics during ageing of the endocrine system","volume":"40","author":"Chen","year":"2021","journal-title":"EMBO J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"eabd7819","DOI":"10.1126\/sciadv.abd7819","article-title":"High-resolution 3D imaging uncovers organ-specific vascular control of tissue aging","volume":"7","author":"Chen","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3125","DOI":"10.1161\/01.CIR.99.24.3125","article-title":"PPARalpha activators inhibit cytokine-induced vascular cell adhesion molecule-1 expression in human endothelial cells","volume":"99","author":"Marx","year":"1999","journal-title":"Circulation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"25573","DOI":"10.1074\/jbc.273.40.25573","article-title":"Activation of proliferator-activated receptors alpha and gamma induces apoptosis of human monocyte-derived macrophages","volume":"273","author":"Chinetti","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"32048","DOI":"10.1074\/jbc.274.45.32048","article-title":"Peroxisome proliferator-activated receptor alpha negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-kappaB and AP-1","volume":"274","author":"Delerive","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/31701","article-title":"Activation of human aortic smooth-muscle cells is inhibited by PPARalpha but not by PPARgamma activators","volume":"393","author":"Staels","year":"1998","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1161\/01.CIR.103.2.207","article-title":"PPARalpha agonists inhibit tissue factor expression in human monocytes and macrophages","volume":"103","author":"Neve","year":"2001","journal-title":"Circulation"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1097\/00005344-200212000-00003","article-title":"Peroxisome proliferator-activated receptor activators inhibit oxidized low-density lipoprotein-induced endothelin-1 secretion in endothelial cells","volume":"40","author":"Furman","year":"2002","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/S0014-5793(00)02351-6","article-title":"Eicosapentaenoic acid (EPA) induces Ca(2+)-independent activation and translocation of endothelial nitric oxide synthase and endothelium-dependent vasorelaxation","volume":"487","author":"Omura","year":"2001","journal-title":"FEBS Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1161\/01.ATV.0000118682.58708.78","article-title":"Peroxisome proliferator-activated receptor alpha agonists increase nitric oxide synthase expression in vascular endothelial cells","volume":"24","author":"Goya","year":"2004","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1007\/s00018-003-2322-6","article-title":"Fenofibrate inhibits angiogenesis in vitro and in vivo","volume":"60","author":"Varet","year":"2003","journal-title":"Cell Mol. Life Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1158\/1535-7163.MCT-06-0722","article-title":"Clofibric acid, a peroxisome proliferator-activated receptor alpha ligand, inhibits growth of human ovarian cancer","volume":"6","author":"Yokoyama","year":"2007","journal-title":"Mol. Cancer Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1111\/j.1365-2230.2011.04125.x","article-title":"Peroxisome proliferator activated receptor-\u03b1 agonists suppress transforming growth factor-\u03b1-induced matrix metalloproteinase-9 expression in human keratinocytes","volume":"36","author":"Meissner","year":"2011","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1073\/pnas.0711281105","article-title":"PPARalpha agonist fenofibrate suppresses tumor growth through direct and indirect angiogenesis inhibition","volume":"105","author":"Panigrahy","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1172\/JCI0214080","article-title":"The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus","volume":"109","author":"Finck","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_28","first-page":"3930","article-title":"Nuclear receptors PPARbeta\/delta and PPARalpha direct distinct metabolic regulatory programs in the mouse heart","volume":"117","author":"Burkart","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1016\/S0140-6736(05)67667-2","article-title":"Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): Randomised controlled trial","volume":"366","author":"Keech","year":"2005","journal-title":"Lancet"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1056\/NEJMoa1001282","article-title":"Effects of combination lipid therapy in type 2 diabetes mellitus","volume":"362","author":"Ginsberg","year":"2010","journal-title":"N Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"771","DOI":"10.2337\/db19-0973","article-title":"Polymorphism Influences the Cardiovascular Benefit of Fenofibrate in Type 2 Diabetes: Findings From ACCORD-Lipid","volume":"69","author":"Morieri","year":"2020","journal-title":"Diabetes"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"293","DOI":"10.2217\/pgs-2019-0140","article-title":"Fibrate pharmacogenomics: Expanding past the genome","volume":"21","author":"House","year":"2020","journal-title":"Pharmacogenomics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1056\/NEJM198711123172001","article-title":"Helsinki Heart Study: Primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease","volume":"317","author":"Frick","year":"1987","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1056\/NEJM199908053410604","article-title":"Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group","volume":"341","author":"Rubins","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/S0002-9149(96)00369-4","article-title":"The Veterans Affairs High-Density Lipoprotein Intervention Trial: Baseline characteristics of normocholesterolemic men with coronary artery disease and low levels of high-density lipoprotein cholesterol. Veterans Affairs Cooperative Studies Program High-Density Lipoprotein Intervention Trial Study Group","volume":"78","author":"Rubins","year":"1996","journal-title":"Am. J. Cardiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.ahj.2018.09.011","article-title":"Rationale and design of the Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT) study","volume":"206","author":"Pradhan","year":"2018","journal-title":"Am. Heart J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0014-2999(01)01589-8","article-title":"PPARalpha and PPARdelta activators inhibit cytokine-induced nuclear translocation of NF-kappaB and expression of VCAM-1 in EAhy926 endothelial cells","volume":"435","author":"Rival","year":"2002","journal-title":"Eur. J. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1161\/ATVBAHA.107.149815","article-title":"Suppression of pro-inflammatory adhesion molecules by PPAR-delta in human vascular endothelial cells","volume":"28","author":"Fan","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1189\/jlb.0508284","article-title":"Activation of PPARbeta\/delta inhibits leukocyte recruitment, cell adhesion molecule expression, and chemokine release","volume":"86","author":"Piqueras","year":"2009","journal-title":"J. Leukoc. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.pharmthera.2005.08.007","article-title":"Peroxisome proliferator-activated receptors and inflammation","volume":"110","author":"Moraes","year":"2006","journal-title":"Pharmacol. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1126\/science.1087344","article-title":"Transcriptional repression of atherogenic inflammation: Modulation by PPARdelta","volume":"302","author":"Lee","year":"2003","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1161\/CIRCRESAHA.107.158477","article-title":"Transforming growth factor-beta1 is a molecular target for the peroxisome proliferator-activated receptor delta","volume":"102","author":"Kim","year":"2008","journal-title":"Circ. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1093\/cvr\/cvp365","article-title":"PPARdelta and PGC1alpha act cooperatively to induce haem oxygenase-1 and enhance vascular endothelial cell resistance to stress","volume":"85","author":"Ali","year":"2010","journal-title":"Cardiovasc. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1161\/01.ATV.0000223875.14120.93","article-title":"Protection of endothelial survival by peroxisome proliferator-activated receptor-delta mediated 14-3-3 upregulation","volume":"26","author":"Liou","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1161\/01.ATV.0000250972.83623.61","article-title":"Activation of PPARbeta\/delta induces endothelial cell proliferation and angiogenesis","volume":"27","author":"Piqueras","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"825970","DOI":"10.1155\/2008\/825970","article-title":"A Role for PPARbeta\/delta in Ocular Angiogenesis","volume":"2008","year":"2008","journal-title":"PPAR Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"E297","DOI":"10.1152\/ajpendo.00581.2007","article-title":"Pharmacological activation of PPARbeta promotes rapid and calcineurin-dependent fiber remodeling and angiogenesis in mouse skeletal muscle","volume":"295","author":"Gaudel","year":"2008","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1093\/cvr\/cvp106","article-title":"Peroxisome proliferator-activated receptor beta stimulation induces rapid cardiac growth and angiogenesis via direct activation of calcineurin","volume":"83","author":"Wagner","year":"2009","journal-title":"Cardiovasc. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"7631085","DOI":"10.1155\/2016\/7631085","article-title":"Inducible Conditional Vascular-Specific Overexpression of Peroxisome Proliferator-Activated Receptor Beta\/Delta Leads to Rapid Cardiac Hypertrophy","volume":"2016","author":"Wagner","year":"2016","journal-title":"PPAR Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Wagner, K.-D., Du, S., Martin, L., Leccia, N., Michiels, J.-F., and Wagner, N. (2019). Vascular PPAR\u03b2\/\u03b4 Promotes Tumor Angiogenesis and Progression. Cells, 8.","DOI":"10.3390\/cells8121623"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"12890","DOI":"10.1073\/pnas.0705505104","article-title":"Transcriptional network governing the angiogenic switch in human pancreatic cancer","volume":"104","author":"Abdollahi","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3686","DOI":"10.1038\/sj.emboj.7601803","article-title":"Deregulation of tumor angiogenesis and blockade of tumor growth in PPARbeta-deficient mice","volume":"26","author":"Rieck","year":"2007","journal-title":"EMBO J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"42397","DOI":"10.1074\/jbc.M506724200","article-title":"Proteomic analysis of vascular endothelial growth factor-induced endothelial cell differentiation reveals a role for chloride intracellular channel 4 (CLIC4) in tubular morphogenesis","volume":"280","author":"Bohman","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1161\/01.RES.0000060700.55247.7C","article-title":"Peroxisome proliferator-activated receptor (PPAR) alpha and PPARbeta\/delta, but not PPARgamma, modulate the expression of genes involved in cardiac lipid metabolism","volume":"92","author":"Gilde","year":"2003","journal-title":"Circ. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1038\/cr.2017.84","article-title":"Live cell screening platform identifies PPAR\u03b4 as a regulator of cardiomyocyte proliferation and cardiac repair","volume":"27","author":"Magadum","year":"2017","journal-title":"Cell Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1097\/FJC.0b013e31804b4163","article-title":"PPARdelta activation normalizes cardiac substrate metabolism and reduces right ventricular hypertrophy in congestive heart failure","volume":"50","author":"Jucker","year":"2007","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1042\/CS20100466","article-title":"Remote preconditioning provides potent cardioprotection via PI3K\/Akt activation and is associated with nuclear accumulation of \u03b2-catenin","volume":"120","author":"Li","year":"2011","journal-title":"Clin. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Park, J.R., Ahn, J.H., Jung, M.H., Koh, J.S., Park, Y., Hwang, S.J., Jeong, Y.H., Kwak, C.H., Lee, Y.S., and Seo, H.G. (2016). Effects of Peroxisome Proliferator-Activated Receptor-\u03b4 Agonist on Cardiac Healing after Myocardial Infarction. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0148510"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/hr.2013.157","article-title":"Telmisartan activates endogenous peroxisome proliferator-activated receptor-\u03b4 and may have anti-fibrotic effects in human mesangial cells","volume":"37","author":"Mikami","year":"2014","journal-title":"Hypertens. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/hr.2012.17","article-title":"Structural basis for telmisartan-mediated partial activation of PPAR gamma","volume":"35","author":"Amano","year":"2012","journal-title":"Hypertens. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1161\/01.HYP.0000123072.34629.57","article-title":"Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARgamma-modulating activity","volume":"43","author":"Benson","year":"2004","journal-title":"Hypertension"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1161\/CIRCULATIONAHA.111.086660","article-title":"Impact of sex on cardiovascular outcome in patients at high cardiovascular risk: Analysis of the Telmisartan Randomized Assessment Study in ACE-Intolerant Subjects With Cardiovascular Disease (TRANSCEND) and the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET)","volume":"126","author":"Kappert","year":"2012","journal-title":"Circulation"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1006\/bbrc.2001.4628","article-title":"Dual function of troglitazone in ICAM-1 gene expression in human vascular endothelium","volume":"282","author":"Chen","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1161\/01.RES.83.11.1097","article-title":"Peroxisome proliferator-activated receptor gamma activators inhibit gene expression and migration in human vascular smooth muscle cells","volume":"83","author":"Marx","year":"1998","journal-title":"Circ. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0014-5793(99)00765-6","article-title":"Thiazolidinedione inhibits the production of monocyte chemoattractant protein-1 in cytokine-treated human vascular endothelial cells","volume":"454","author":"Murao","year":"1999","journal-title":"FEBS Lett."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"6503","DOI":"10.4049\/jimmunol.164.12.6503","article-title":"Peroxisome proliferator-activated receptor-gamma activators inhibit IFN-gamma-induced expression of the T cell-active CXC chemokines IP-10, Mig, and I-TAC in human endothelial cells","volume":"164","author":"Marx","year":"2000","journal-title":"J. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1161\/01.RES.87.6.516","article-title":"Role for peroxisome proliferator-activated receptor alpha in oxidized phospholipid-induced synthesis of monocyte chemotactic protein-1 and interleukin-8 by endothelial cells","volume":"87","author":"Lee","year":"2000","journal-title":"Circ. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/34178","article-title":"The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation","volume":"391","author":"Ricote","year":"1998","journal-title":"Nature"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"9116","DOI":"10.1074\/jbc.274.13.9116","article-title":"Peroxisome proliferator-activated receptor gamma ligands are potent inhibitors of angiogenesis in vitro and in vivo","volume":"274","author":"Xin","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1007\/s10456-005-9027-4","article-title":"PPAR gamma represses VEGF expression in human endometrial cells: Implications for uterine angiogenesis","volume":"8","author":"Peeters","year":"2005","journal-title":"Angiogenesis"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.2337\/diabetes.53.5.1222","article-title":"Bifunctional properties of peroxisome proliferator-activated receptor gamma1 in KDR gene regulation mediated via interaction with both Sp1 and Sp3","volume":"53","author":"Sassa","year":"2004","journal-title":"Diabetes"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"13503","DOI":"10.1074\/jbc.M510357200","article-title":"Antiangiogenic effect of rosiglitazone is mediated via peroxisome proliferator-activated receptor gamma-activated maxi-K channel opening in human umbilical vein endothelial cells","volume":"281","author":"Kim","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_73","first-page":"217","article-title":"The MAPK-dependent regulation of the Jagged\/Notch gene expression by VEGF, bFGF or PPAR gamma mediated angiogenesis in HUVEC","volume":"61","author":"Polus","year":"2010","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1093\/cvr\/cvp400","article-title":"PPARgamma agonists inhibit angiogenesis by suppressing PKCalpha- and CREB-mediated COX-2 expression in the human endothelium","volume":"86","author":"Scoditti","year":"2010","journal-title":"Cardiovasc. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.mce.2013.07.011","article-title":"Cilostazol improves the response to ischemia in diabetic mice by a mechanism dependent on PPAR\u03b3","volume":"381","author":"Biscetti","year":"2013","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.biopha.2007.06.014","article-title":"Pioglitazone ameliorates endothelial dysfunction and restores ischemia-induced angiogenesis in diabetic mice","volume":"62","author":"Huang","year":"2008","journal-title":"Biomed. Pharmacother."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.brainres.2006.03.114","article-title":"Peroxisome proliferator-activated receptor-gamma-agonist, rosiglitazone, promotes angiogenesis after focal cerebral ischemia","volume":"1093","author":"Chu","year":"2006","journal-title":"Brain Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1161\/01.RES.0000179226.34112.6d","article-title":"Cardiomyocyte-specific knockout and agonist of peroxisome proliferator-activated receptor-gamma both induce cardiac hypertrophy in mice","volume":"97","author":"Duan","year":"2005","journal-title":"Circ. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1172\/JCI30335","article-title":"Cardiomyocyte expression of PPARgamma leads to cardiac dysfunction in mice","volume":"117","author":"Son","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.atherosclerosis.2018.05.005","article-title":"Myeloid peroxisome proliferator-activated receptor gamma deficiency aggravates myocardial infarction in mice","volume":"274","author":"Shen","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"591","DOI":"10.4070\/kcj.2017.0029","article-title":"Effect of Pioglitazone in Combination with Moderate Dose Statin on Atherosclerotic Inflammation: Randomized Controlled Clinical Trial Using Serial FDG-PET\/CT","volume":"48","author":"Choo","year":"2018","journal-title":"Korean Circ. J."},{"key":"ref_82","first-page":"881","article-title":"Effect of pioglitazone on insulin resistance, progression of atherosclerosis and clinical course of coronary heart disease","volume":"70","author":"Skochko","year":"2017","journal-title":"Wiad. Lek."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1055\/s-2005-870322","article-title":"Pharmacological PPARgamma stimulation in contrast to beta cell stimulation results in an improvement in adiponectin and proinsulin intact levels and reduces intima media thickness in patients with type 2 diabetes","volume":"37","author":"Forst","year":"2005","journal-title":"Horm. Metab. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e123","DOI":"10.1016\/j.atherosclerosis.2006.11.007","article-title":"Fenofibrate and pioglitazone improve endothelial function and reduce arterial stiffness in obese glucose tolerant men","volume":"194","author":"Ryan","year":"2007","journal-title":"Atherosclerosis"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"187","DOI":"10.2165\/00002018-200932030-00002","article-title":"Safety and tolerability of pioglitazone in high-risk patients with type 2 diabetes: An overview of data from PROactive","volume":"32","author":"Dormandy","year":"2009","journal-title":"Drug Saf."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1016\/S0140-6736(05)67528-9","article-title":"Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): A randomised controlled trial","volume":"366","author":"Dormandy","year":"2005","journal-title":"Lancet"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2773","DOI":"10.2337\/dc07-0717","article-title":"Pioglitazone use and heart failure in patients with type 2 diabetes and preexisting cardiovascular disease: Data from the PROactive study (PROactive 08)","volume":"30","author":"Erdmann","year":"2007","journal-title":"Diabetes Care"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1001\/jama.299.13.1561","article-title":"Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: The PERISCOPE randomized controlled trial","volume":"299","author":"Nissen","year":"2008","journal-title":"JAMA"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1056\/NEJMoa1506930","article-title":"Pioglitazone after Ischemic Stroke or Transient Ischemic Attack","volume":"374","author":"Kernan","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/pds.4154","article-title":"Pioglitazone and bladder cancer: FDA\u2019s assessment","volume":"26","author":"Hampp","year":"2017","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1016\/S0140-6736(06)69420-8","article-title":"Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: A randomised controlled trial","volume":"368","author":"Gerstein","year":"2006","journal-title":"Lancet"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1056\/NEJMoa066224","article-title":"Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy","volume":"355","author":"Kahn","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1056\/NEJMoa072761","article-title":"Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes","volume":"356","author":"Nissen","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1016\/S0140-6736(09)60953-3","article-title":"Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): A multicentre, randomised, open-label trial","volume":"373","author":"Home","year":"2009","journal-title":"Lancet"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1056\/NEJMp1008233","article-title":"Revisiting the rosiglitazone story--lessons learned","volume":"363","author":"Rosen","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1161\/01.ATV.0000147897.57527.e4","article-title":"Cardiovascular risk in type 2 diabetes is associated with variation at the PPARG locus: A Go-DARTS study","volume":"24","author":"Doney","year":"2004","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"276581","DOI":"10.1155\/2008\/276581","article-title":"Genetic polymorphisms of peroxisome proliferator-activated receptors and the risk of cardiovascular morbidity and mortality in a community-based cohort in washington county, Maryland","volume":"2008","author":"Gallicchio","year":"2008","journal-title":"PPAR Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1475-2840-4-14","article-title":"Dual and pan-peroxisome proliferator-activated receptors (PPAR) co-agonism: The bezafibrate lessons","volume":"4","author":"Tenenbaum","year":"2005","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"641","DOI":"10.2337\/diacare.21.4.641","article-title":"Cardiovascular outcomes in type 2 diabetes. A double-blind placebo-controlled study of bezafibrate: The St. Mary\u2019s, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention (SENDCAP) Study","volume":"21","author":"Elkeles","year":"1998","journal-title":"Diabetes Care"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"The BIP Study Group (2000). Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease. Circulation, 102, 21\u201327.","DOI":"10.1161\/01.CIR.102.1.21"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1001\/jama.294.20.joc50147","article-title":"Effect of muraglitazar on death and major adverse cardiovascular events in patients with type 2 diabetes mellitus","volume":"294","author":"Nissen","year":"2005","journal-title":"JAMA"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1080\/01926230500214657","article-title":"Generalized cellular hypertrophy is induced by a dual-acting PPAR agonist in rat urinary bladder urothelium in vivo","volume":"33","author":"Oleksiewicz","year":"2005","journal-title":"Toxicol Pathol"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"214","DOI":"10.3132\/dvdr.2007.042","article-title":"Efficacy, safety and tolerability of tesaglitazar when added to the therapeutic regimen of poorly controlled insulin-treated patients with type 2 diabetes","volume":"4","author":"Ratner","year":"2007","journal-title":"Diab. Vasc. Dis. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/S0140-6736(09)60870-9","article-title":"Effect of the dual peroxisome proliferator-activated receptor-alpha\/gamma agonist aleglitazar on risk of cardiovascular disease in patients with type 2 diabetes (SYNCHRONY): A phase II, randomised, dose-ranging study","volume":"374","author":"Henry","year":"2009","journal-title":"Lancet"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1001\/jama.2014.3321","article-title":"Effect of aleglitazar on cardiovascular outcomes after acute coronary syndrome in patients with type 2 diabetes mellitus: The AleCardio randomized clinical trial","volume":"311","author":"Lincoff","year":"2014","journal-title":"JAMA"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.ahj.2015.03.021","article-title":"Effects of the dual peroxisome proliferator-activated receptor activator aleglitazar in patients with Type 2 Diabetes mellitus or prediabetes","volume":"170","author":"Erdmann","year":"2015","journal-title":"Am. Heart J."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1016\/j.amjcard.2020.12.022","article-title":"Aspirin for Primary Prevention of Cardiovascular Disease in the 21","volume":"144","author":"Angiolillo","year":"2021","journal-title":"Am. J. Cardiol."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Kolawole, O.R., and Kashfi, K. (2022). NSAIDs and Cancer Resolution: New Paradigms beyond Cyclooxygenase. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031432"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"E7408","DOI":"10.1073\/pnas.1802021115","article-title":"Aspirin binds to PPAR\u03b1 to stimulate hippocampal plasticity and protect memory","volume":"115","author":"Patel","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1002\/jnr.24561","article-title":"PPAR\u03b1 serves as a new receptor of aspirin for neuroprotection","volume":"98","author":"Patel","year":"2020","journal-title":"J. Neurosci. Res."},{"key":"ref_111","first-page":"257","article-title":"The metabotrophic NGF and BDNF: An emerging concept","volume":"149","author":"Chaldakov","year":"2011","journal-title":"Arch. Ital. Biol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/j.jacc.2005.02.094","article-title":"Aspirin, but not clopidogrel, reduces collateral conductance in a rabbit model of femoral artery occlusion","volume":"46","author":"Hoefer","year":"2005","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1096\/fj.06-5987com","article-title":"Therapeutic levels of aspirin and salicylate directly inhibit a model of angiogenesis through a Cox-independent mechanism","volume":"20","author":"Borthwick","year":"2006","journal-title":"FASEB J."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"4256","DOI":"10.1096\/fj.201600530R","article-title":"Aspirin inhibits the production of proangiogenic 15(S)-HETE by platelet cyclooxygenase-1","volume":"30","author":"Rauzi","year":"2016","journal-title":"FASEB J."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Wu, L., Wang, W., Dai, M., Li, H., Chen, C., and Wang, D. (2019). PPAR\u03b1 ligand, AVE8134, and cyclooxygenase inhibitor therapy synergistically suppress lung cancer growth and metastasis. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-6379-5"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ijcard.2003.03.007","article-title":"Aspirin decreases vascular endothelial growth factor release during myocardial ischemia","volume":"94","author":"Gerrah","year":"2004","journal-title":"Int. J. Cardiol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/0014-5793(76)80996-9","article-title":"Competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase by ML-236A and ML-236B fungal metabolites, having hypocholesterolemic activity","volume":"72","author":"Endo","year":"1976","journal-title":"FEBS Lett."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Nowak, M.M., Niemczyk, M., Florczyk, M., Kurzyna, M., and P\u0105czek, L. (2022). Effect of Statins on All-Cause Mortality in Adults: A Systematic Review and Meta-Analysis of Propensity Score-Matched Studies. J. Clin. Med., 11.","DOI":"10.3390\/jcm11195643"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1161\/01.RES.0000268411.49545.9c","article-title":"Statins activate peroxisome proliferator-activated receptor gamma through extracellular signal-regulated kinase 1\/2 and p38 mitogen-activated protein kinase-dependent cyclooxygenase-2 expression in macrophages","volume":"100","author":"Yano","year":"2007","journal-title":"Circ. Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1161\/01.RES.0000202706.70992.95","article-title":"Acute antiinflammatory properties of statins involve peroxisome proliferator-activated receptor-alpha via inhibition of the protein kinase C signaling pathway","volume":"98","author":"Paumelle","year":"2006","journal-title":"Circ. Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/S0024-3205(00)00680-9","article-title":"Lipophilic HMG-CoA reductase inhibitor has an anti-inflammatory effect: Reduction of MRNA levels for interleukin-1beta, interleukin-6, cyclooxygenase-2, and p22phox by regulation of peroxisome proliferator-activated receptor alpha (PPARalpha) in primary endothelial cells","volume":"67","author":"Inoue","year":"2000","journal-title":"Life Sci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1172\/JCI10852","article-title":"Statin-induced inhibition of the Rho-signaling pathway activates PPARalpha and induces HDL apoA-I","volume":"107","author":"Martin","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_123","first-page":"365","article-title":"Atorvastatin attenuating down-regulation of peroxisome proliferator-activated receptor gamma in preventing cardiac hypertrophy of rats in vitro and in vivo","volume":"9","author":"Ye","year":"2006","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1038\/aps.2010.109","article-title":"Simvastatin inhibited cardiac hypertrophy and fibrosis in apolipoprotein E-deficient mice fed a \u201cWestern-style diet\u201d by increasing PPAR \u03b1 and \u03b3 expression and reducing TC, MMP-9, and Cat S levels","volume":"31","author":"Qin","year":"2010","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.ejphar.2010.08.058","article-title":"Simvastatin attenuates cardiopulmonary bypass-induced myocardial inflammatory injury in rats by activating peroxisome proliferator-activated receptor \u03b3","volume":"649","author":"Shen","year":"2010","journal-title":"Eur. J. Pharmacol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1093\/eurheartj\/ehm540","article-title":"Rosuvastatin increases vascular endothelial PPARgamma expression and corrects blood pressure variability in obese dyslipidaemic mice","volume":"29","author":"Desjardins","year":"2008","journal-title":"Eur. Heart J."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1161\/ATVBAHA.108.183160","article-title":"Antiplatelet actions of statins and fibrates are mediated by PPARs","volume":"29","author":"Ali","year":"2009","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1161\/hc0602.103393","article-title":"Statins have biphasic effects on angiogenesis","volume":"105","author":"Weis","year":"2002","journal-title":"Circulation"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1080\/10623320500476559","article-title":"Atorvastatin affects several angiogenic mediators in human endothelial cells","volume":"12","author":"Dulak","year":"2005","journal-title":"Endothelium"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1161\/01.RES.0000014081.30867.F8","article-title":"Double-edged role of statins in angiogenesis signaling","volume":"90","author":"Urbich","year":"2002","journal-title":"Circ. Res."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"319","DOI":"10.5551\/jat.No026","article-title":"Effects of atorvastatin on angiogenesis in hindlimb ischemia and endothelial progenitor cell formation in rats","volume":"16","author":"Matsumura","year":"2009","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"e91419","DOI":"10.1172\/jci.insight.91419","article-title":"Metastasis regulation by PPARD expression in cancer cells","volume":"2","author":"Zuo","year":"2017","journal-title":"JCI Insight"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1006\/bbrc.2001.6141","article-title":"Fibrate and statin synergistically increase the transcriptional activities of PPARalpha\/RXRalpha and decrease the transactivation of NFkappaB","volume":"290","author":"Inoue","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1152\/physiolgenomics.00062.2002","article-title":"Angiotensin II is associated with activation of NF-kappaB-mediated genes and downregulation of PPARs","volume":"11","author":"Tham","year":"2002","journal-title":"Physiol. Genom."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.atherosclerosis.2004.08.023","article-title":"Enalapril attenuates angiotensin II-induced atherosclerosis and vascular inflammation","volume":"178","author":"Tham","year":"2005","journal-title":"Atherosclerosis"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1111\/j.1365-2362.2008.02025.x","article-title":"Angiotensin inhibition stimulates PPARgamma and the release of visfatin","volume":"38","author":"Storka","year":"2008","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"e107","DOI":"10.1159\/000104834","article-title":"PPAR-gamma activation inhibits angiotensin II synthesis, apoptosis, and proliferation of mesangial cells from spontaneously hypertensive rats","volume":"106","author":"Efrati","year":"2007","journal-title":"Nephron. Exp. Nephrol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.ejphar.2016.08.040","article-title":"Ramipril restores PPAR\u03b2\/\u03b4 and PPAR\u03b3 expressions and reduces cardiac NADPH oxidase but fails to restore cardiac function and accompanied myosin heavy chain ratio shift in severe anthracycline-induced cardiomyopathy in rat","volume":"791","author":"Cernecka","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1161\/hy0302.104671","article-title":"Endothelial nitric oxide synthase lies downstream from angiotensin II-induced angiogenesis in ischemic hindlimb","volume":"39","author":"Tamarat","year":"2002","journal-title":"Hypertension"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"H1387","DOI":"10.1152\/ajpheart.00299.2002","article-title":"Role of ANG II in coronary capillary angiogenesis at the insulin-resistant stage of a NIDDM rat model","volume":"283","author":"Jesmin","year":"2002","journal-title":"Am. J. Physiol. Heart. Circ. Physiol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1096\/fj.03-0129com","article-title":"Differential regulation of in vivo angiogenesis by angiotensin II receptors","volume":"17","author":"Walther","year":"2003","journal-title":"FASEB J."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"223","DOI":"10.2174\/1570161112666140226121627","article-title":"Kinin receptors in vascular biology and pathology","volume":"12","author":"Couture","year":"2014","journal-title":"Curr. Vasc. Pharmacol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"3043","DOI":"10.1161\/01.CIR.99.23.3043","article-title":"Tissue inhibition of angiotensin-converting enzyme activity stimulates angiogenesis in vivo","volume":"99","author":"Fabre","year":"1999","journal-title":"Circulation"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1161\/hh2001.097691","article-title":"Proangiogenic effect of angiotensin-converting enzyme inhibition is mediated by the bradykinin B(2) receptor pathway","volume":"89","author":"Silvestre","year":"2001","journal-title":"Circ. Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1161\/HYPERTENSIONAHA.107.097394","article-title":"Role of bradykinin, nitric oxide, and angiotensin II type 2 receptor in imidapril-induced angiogenesis","volume":"51","author":"Li","year":"2008","journal-title":"Hypertension"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1161\/01.HYP.20.4.478","article-title":"Effect of early onset angiotensin converting enzyme inhibition on myocardial capillaries","volume":"20","author":"Unger","year":"1992","journal-title":"Hypertension"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1093\/cvr\/cvn170","article-title":"B2-kinin receptor plays a key role in B1-, angiotensin converting enzyme inhibitor-, and vascular endothelial growth factor-stimulated in vitro angiogenesis in the hypoxic mouse heart","volume":"80","author":"Neysari","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.mvr.2010.05.007","article-title":"Tissue ACE inhibition improves microcirculation in remote myocardium after coronary stenosis: MR imaging study in rats","volume":"80","author":"Hiller","year":"2010","journal-title":"Microvasc. Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1097\/01.hjh.0000170387.61579.ab","article-title":"Long-term exercise training and angiotensin-converting enzyme inhibition differentially enhance myocardial capillarization in the spontaneously hypertensive rat","volume":"23","author":"Ziada","year":"2005","journal-title":"J. Hypertens."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1161\/01.ATV.0000149377.90852.d8","article-title":"Dual effect of angiotensin-converting enzyme inhibition on angiogenesis in type 1 diabetic mice","volume":"25","author":"Ebrahimian","year":"2005","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_151","first-page":"720","article-title":"Localization of angiotensin converting enzyme in rabbit cornea and its role in controlling corneal angiogenesis in vivo","volume":"16","author":"Sharma","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"H1163","DOI":"10.1152\/ajpheart.2001.281.3.H1163","article-title":"Angiotensin II and VEGF are involved in angiogenesis induced by short-term exercise training","volume":"281","author":"Amaral","year":"2001","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1172\/JCI118838","article-title":"Captopril inhibits angiogenesis and slows the growth of experimental tumors in rats","volume":"98","author":"Volpert","year":"1996","journal-title":"J. Clin. Investig."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.jhep.2004.12.025","article-title":"Combination of vitamin K2 and the angiotensin-converting enzyme inhibitor, perindopril, attenuates the liver enzyme-altered preneoplastic lesions in rats via angiogenesis suppression","volume":"42","author":"Yoshiji","year":"2005","journal-title":"J. Hepatol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1196\/annals.1414.011","article-title":"Captopril as a potential inhibitor of lung tumor growth and metastasis","volume":"1138","author":"Attoub","year":"2008","journal-title":"Ann. N Y Acad. Sci."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.amjcard.2011.03.038","article-title":"Meta-analysis of randomized controlled trials on effect of angiotensin-converting enzyme inhibitors on cancer risk","volume":"108","author":"Sipahi","year":"2011","journal-title":"Am. J. Cardiol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"107527","DOI":"10.1016\/j.pharmthera.2020.107527","article-title":"Evaluating the benefits of renin-angiotensin system inhibitors as cancer treatments","volume":"211","author":"Perini","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/S0140-6736(99)10365-9","article-title":"Angiotensin II receptor antagonists","volume":"355","author":"Burnier","year":"2000","journal-title":"Lancet"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1161\/01.CIR.0000127955.36250.65","article-title":"Angiotensin type 1 receptor blockers induce peroxisome proliferator-activated receptor-gamma activity","volume":"109","author":"Schupp","year":"2004","journal-title":"Circulation"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1517\/14656566.5.11.2397","article-title":"Telmisartan-killing two birds with one stone","volume":"5","author":"Doggrell","year":"2004","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.cardiores.2006.07.014","article-title":"Telmisartan downregulates angiotensin II type 1 receptor through activation of peroxisome proliferator-activated receptor gamma","volume":"72","author":"Imayama","year":"2006","journal-title":"Cardiovasc. Res."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1291\/hypres.30.1231","article-title":"Inhibition of vascular angiotensin-converting enzyme by telmisartan via the peroxisome proliferator-activated receptor gamma agonistic property in rats","volume":"30","author":"Takai","year":"2007","journal-title":"Hypertens. Res."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.atherosclerosis.2007.10.037","article-title":"Anti-atherosclerotic properties of telmisartan in advanced atherosclerotic lesions in apolipoprotein E deficient mice","volume":"199","author":"Blessing","year":"2008","journal-title":"Atherosclerosis"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.atherosclerosis.2008.12.036","article-title":"Telmisartan induces proliferation of human endothelial progenitor cells via PPARgamma-dependent PI3K\/Akt pathway","volume":"205","author":"Honda","year":"2009","journal-title":"Atherosclerosis"},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Zeng, X.C., Li, X.S., and Wen, H. (2013). Telmisartan protects against microvascular dysfunction during myocardial ischemia\/reperfusion injury by activation of peroxisome proliferator-activated receptor \u03b3. BMC Cardiovasc. Disord., 13.","DOI":"10.1186\/1471-2261-13-39"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.bbrc.2011.02.007","article-title":"Irbesartan increased PPAR\u03b3 activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction","volume":"406","author":"Iwai","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1254\/jphs.11053FP","article-title":"Irbesartan prevents metabolic syndrome in rats via activation of peroxisome proliferator-activated receptor \u03b3","volume":"116","author":"Takai","year":"2011","journal-title":"J. Pharmacol. Sci."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1038\/npp.2012.152","article-title":"Candesartan, an angiotensin II AT\u2081-receptor blocker and PPAR-\u03b3 agonist, reduces lesion volume and improves motor and memory function after traumatic brain injury in mice","volume":"37","author":"Villapol","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1111\/bph.12229","article-title":"Losartan protects liver against ischaemia\/reperfusion injury through PPAR-\u03b3 activation and receptor for advanced glycation end-products down-regulation","volume":"169","author":"Koh","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1186\/1479-5876-11-229","article-title":"Cardiac protective effects of irbesartan via the PPAR-gamma signaling pathway in angiotensin-converting enzyme 2-deficient mice","volume":"11","author":"Zhang","year":"2013","journal-title":"J Transl Med"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.intimp.2016.11.015","article-title":"Irbesartan ameliorates hyperlipidemia and liver steatosis in type 2 diabetic db\/db mice via stimulating PPAR-\u03b3, AMPK\/Akt\/mTOR signaling and autophagy","volume":"42","author":"Zhong","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3892\/mmr.2022.12834","article-title":"Angiotensin II receptor type 1 blocker candesartan improves morphine tolerance by reducing morphine-induced inflammatory response and cellular activation of BV2 cells via the PPAR\u03b3\/AMPK signaling pathway","volume":"26","author":"Zhao","year":"2022","journal-title":"Mol. Med. Rep."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.2337\/db07-0839","article-title":"Liver-specific peroxisome proliferator-activated receptor alpha target gene regulation by the angiotensin type 1 receptor blocker telmisartan","volume":"57","author":"Clemenz","year":"2008","journal-title":"Diabetes"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1111\/j.1476-5381.2010.00835.x","article-title":"Irbesartan treatment up-regulates hepatic expression of PPARalpha and its target genes in obese Koletsky (fa(k)\/fa(k)) rats: A link to amelioration of hypertriglyceridaemia","volume":"160","author":"Rong","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1097\/HJH.0b013e32834c46fd","article-title":"Molecular and cellular effects of azilsartan: A new generation angiotensin II receptor blocker","volume":"29","author":"Kajiya","year":"2011","journal-title":"J. Hypertens."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1042\/CS20160343","article-title":"Peroxisome proliferator-activated receptor \u03b1-dependent renoprotection of murine kidney by irbesartan","volume":"130","author":"Harada","year":"2016","journal-title":"Clin. Sci."},{"key":"ref_177","first-page":"259","article-title":"Telmisartan is the most effective ARB to increase adiponectin via PPAR\u03b1 in adipocytes","volume":"69","author":"Hattori","year":"2022","journal-title":"J. Mol. Endocrinol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"762","DOI":"10.2337\/db12-0570","article-title":"Telmisartan improves insulin resistance of skeletal muscle through peroxisome proliferator-activated receptor-\u03b4 activation","volume":"62","author":"Li","year":"2013","journal-title":"Diabetes"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s12933-016-0430-5","article-title":"Telmisartan improves cardiac fibrosis in diabetes through peroxisome proliferator activated receptor \u03b4 (PPAR\u03b4): From bedside to bench","volume":"15","author":"Chang","year":"2016","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"828","DOI":"10.3892\/ijmm.2014.1834","article-title":"Telmisartan inhibits the proinflammatory effects of homocysteine on human endothelial cells through activation of the peroxisome proliferator-activated receptor-\u03b4 pathway","volume":"34","author":"Xu","year":"2014","journal-title":"Int. J. Mol. Med."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1161\/HYPERTENSIONAHA.109.143958","article-title":"Telmisartan prevents weight gain and obesity through activation of peroxisome proliferator-activated receptor-delta-dependent pathways","volume":"55","author":"He","year":"2010","journal-title":"Hypertension"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ejphar.2016.02.042","article-title":"Inhibition of endoplasmic reticulum stress-activated IRE1\u03b1-TRAF2-caspase-12 apoptotic pathway is involved in the neuroprotective effects of telmisartan in the rotenone rat model of Parkinson\u2019s disease","volume":"776","author":"Tong","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"14021","DOI":"10.1038\/s41598-017-14265-4","article-title":"Telmisartan Activates PPAR\u03b4 to Improve Symptoms of Unpredictable Chronic Mild Stress-Induced Depression in Mice","volume":"7","author":"Li","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/sj.bjp.0704461","article-title":"Angiotensin AT(1) receptor signalling modulates reparative angiogenesis induced by limb ischaemia","volume":"135","author":"Emanueli","year":"2002","journal-title":"Br. J. Pharmacol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0008-6363(02)00843-X","article-title":"VEGF-mediated angiogenesis is impaired by angiotensin type 1 receptor blockade in cardiomyopathic hamster hearts","volume":"58","author":"Shimizu","year":"2003","journal-title":"Cardiovasc. Res."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"H1237","DOI":"10.1152\/ajpheart.00965.2006","article-title":"ANG II type 1 receptor antagonist irbesartan inhibits coronary angiogenesis stimulated by chronic intermittent hypoxia in neonatal rats","volume":"292","author":"Rakusan","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1093\/humrep\/deu035","article-title":"Combined blockade of angiotensin II type 1 receptor and activation of peroxisome proliferator-activated receptor-\u03b3 by telmisartan effectively inhibits vascularization and growth of murine endometriosis-like lesions","volume":"29","author":"Nenicu","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1161\/HYPERTENSIONAHA.109.138750","article-title":"Telmisartan-induced inhibition of vascular cell proliferation beyond angiotensin receptor blockade and peroxisome proliferator-activated receptor-gamma activation","volume":"54","author":"Yamamoto","year":"2009","journal-title":"Hypertension"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/labinvest.3700504","article-title":"Roles for host and tumor angiotensin II type 1 receptor in tumor growth and tumor-associated angiogenesis","volume":"87","author":"Imai","year":"2007","journal-title":"Lab. Investig."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"2686","DOI":"10.1158\/1078-0432.CCR-04-1946","article-title":"Functional expression of the angiotensin II type 1 receptor in human ovarian carcinoma cells and its blockade therapy resulting in suppression of tumor invasion, angiogenesis, and peritoneal dissemination","volume":"11","author":"Suganuma","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"2862","DOI":"10.3390\/molecules19032862","article-title":"Telmisartan exerts anti-tumor effects by activating peroxisome proliferator-activated receptor-\u03b3 in human lung adenocarcinoma A549 cells","volume":"19","author":"Li","year":"2014","journal-title":"Molecules"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"555","DOI":"10.3892\/mmr.2015.4512","article-title":"Telmisartan prevents proliferation and promotes apoptosis of human ovarian cancer cells through upregulating PPAR\u03b3 and downregulating MMP-9 expression","volume":"13","author":"Pu","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/S1470-2045(10)70106-6","article-title":"Angiotensin-receptor blockade and risk of cancer: Meta-analysis of randomised controlled trials","volume":"11","author":"Sipahi","year":"2010","journal-title":"Lancet Oncol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S1470-2045(10)70260-6","article-title":"Antihypertensive drugs and risk of cancer: Network meta-analyses and trial sequential analyses of 324,168 participants from randomised trials","volume":"12","author":"Bangalore","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"ARB Trialists Collaboration (2011). Effects of telmisartan, irbesartan, valsartan, candesartan, and losartan on cancers in 15 trials enrolling 138,769 individuals. J. Hypertens., 29, 623\u2013635.","DOI":"10.1097\/HJH.0b013e328344a7de"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"10674","DOI":"10.1073\/pnas.1819889116","article-title":"Reprogramming the microenvironment with tumor-selective angiotensin blockers enhances cancer immunotherapy","volume":"116","author":"Chauhan","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2345\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:15:13Z","timestamp":1760120113000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2345"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,25]]},"references-count":196,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24032345"],"URL":"https:\/\/doi.org\/10.3390\/ijms24032345","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,25]]}}}