{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:49:45Z","timestamp":1791578985596,"version":"4.3.4"},"reference-count":152,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100016747","name":"Mercer University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016747","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Drug Discovery Today"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1016\/j.drudis.2026.104815","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T07:12:49Z","timestamp":1790320369000},"page":"104815","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["The endothelin system: a potential target for the treatment of type 2 diabetes mellitus and associated cardiometabolic complications"],"prefix":"10.1016","volume":"31","author":[{"given":"Md. Moklesur Rahman","family":"Sarker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Nurul","family":"Islam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nimi P.","family":"Simon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tariful","family":"Islam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.Z.M.","family":"Naser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherif","family":"Hafez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6897-2901","authenticated-orcid":false,"given":"Raquibul","family":"Hasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.drudis.2026.104815_b0005","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0140-6736(23)01301-6","article-title":"Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021","volume":"402","author":"Ong","year":"2023","journal-title":"Lancet"},{"key":"10.1016\/j.drudis.2026.104815_b0010","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/s41586-022-04536-0","article-title":"Obesity alters pathology and treatment response in inflammatory disease","volume":"604","author":"Bapat","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.drudis.2026.104815_b0015","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.125.041834","article-title":"Population\u2010based study on the coexistence of metabolic dysfunction\u2010associated steatotic liver disease and chronic kidney disease","volume":"14","author":"Goh","year":"2025","journal-title":"J Am Heart Assoc"},{"key":"10.1016\/j.drudis.2026.104815_b0020","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3389\/fendo.2017.00006","article-title":"Clinical review of antidiabetic drugs: implications for type 2 diabetes mellitus management","volume":"8","author":"Chaudhury","year":"2017","journal-title":"Front Endocrinol"},{"key":"10.1016\/j.drudis.2026.104815_b0025","article-title":"Pharmacotherapy of type 2 diabetes: an update and future directions","volume":"1","author":"DeMarsilis","year":"2022","journal-title":"Metabolism"},{"key":"10.1016\/j.drudis.2026.104815_b0030","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.2147\/PPA.S106821","article-title":"Poor medication adherence in type 2 diabetes: recognizing the scope of the problem and its key contributors","volume":"10","author":"Polonsky","year":"2016","journal-title":"Patient Prefer Adherence"},{"key":"10.1016\/j.drudis.2026.104815_b0035","doi-asserted-by":"crossref","first-page":"706","DOI":"10.2337\/dc16-1943","article-title":"Sulfonylureas and the risks of cardiovascular events and death: a methodological meta-regression analysis of the observational studies","volume":"40","author":"Azoulay","year":"2017","journal-title":"Diabetes Care"},{"key":"10.1016\/j.drudis.2026.104815_b0040","doi-asserted-by":"crossref","DOI":"10.1016\/j.molmet.2023.101868","article-title":"Endothelin receptor B-deficient mice are protected from high-fat diet-induced metabolic syndrome","volume":"80","author":"Feger","year":"2024","journal-title":"Mol Metab"},{"key":"10.1016\/j.drudis.2026.104815_b0045","doi-asserted-by":"crossref","DOI":"10.1111\/obr.13086","article-title":"Endothelin-1 in the pathophysiology of obesity and insulin resistance","volume":"21","author":"Jenkins","year":"2020","journal-title":"Obes Rev"},{"key":"10.1016\/j.drudis.2026.104815_b0050","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1161\/HYPERTENSIONAHA.119.12105","article-title":"Endothelin: 30 years from discovery to therapy","volume":"74","author":"Barton","year":"2019","journal-title":"Hypertension"},{"key":"10.1016\/j.drudis.2026.104815_b0055","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s00418-002-0457-4","article-title":"Cellular localization of the endothelin receptor subtypes ETA and ETB in the rat heart and their differential expression in coronary arteries, veins, and capillaries","volume":"118","author":"Wendel-Wellner","year":"2002","journal-title":"Histochem Cell Biol"},{"key":"10.1016\/j.drudis.2026.104815_b0060","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1124\/pr.115.011833","article-title":"Endothelin","volume":"68","author":"Davenport","year":"2016","journal-title":"Pharmacol Rev"},{"key":"10.1016\/j.drudis.2026.104815_b0065","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ejphar.2003.12.003","article-title":"Different role of endothelin ETA and ETB receptors and endothelial modulators in diabetes-induced hyperreactivity of the rabbit carotid artery to endothelin-1","volume":"486","author":"Llor\u00e9ns","year":"2004","journal-title":"Eur J Pharmacol"},{"key":"10.1016\/j.drudis.2026.104815_b0070","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1146\/annurev.pharmtox.41.1.851","article-title":"Endothelin system: the double-edged sword in health and disease","volume":"41","author":"Kedzierski","year":"2001","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"10.1016\/j.drudis.2026.104815_b0075","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1038\/ki.2014.143","article-title":"Endothelin and endothelin antagonists in chronic kidney disease","volume":"86","author":"Kohan","year":"2014","journal-title":"Kidney Int"},{"key":"10.1016\/j.drudis.2026.104815_b0080","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/s41581-024-00908-z","article-title":"Endothelin receptor antagonists in chronic kidney disease","volume":"21","author":"Smeijer","year":"2025","journal-title":"Nat Rev Nephrol"},{"key":"10.1016\/j.drudis.2026.104815_b0085","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1016\/S0140-6736(09)60619-X","article-title":"Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study","volume":"373","author":"Tab\u00e1k","year":"2009","journal-title":"Lancet"},{"key":"10.1016\/j.drudis.2026.104815_b0090","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s11154-012-9232-6","article-title":"The endothelial cell: an \u2018early responder\u2019 in the development of insulin resistance","volume":"14","author":"Barrett","year":"2013","journal-title":"Rev Endocr Metab Disord"},{"key":"10.1016\/j.drudis.2026.104815_b0095","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1093\/jmcb\/mjab024","article-title":"Diabetes pathogenesis and management: the endothelium comes of age","volume":"13","author":"Love","year":"2021","journal-title":"J Mol Cell Biol"},{"key":"10.1016\/j.drudis.2026.104815_b0100","doi-asserted-by":"crossref","first-page":"4671","DOI":"10.1007\/s11010-025-05289-w","article-title":"Endothelial dysfunction in cardiovascular diseases: mechanisms and in vitro models","volume":"480","author":"Grego","year":"2025","journal-title":"Mol Cell Biochem"},{"key":"10.1016\/j.drudis.2026.104815_b0105","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/bs.apha.2016.05.002","article-title":"Endothelin-1: biosynthesis, signaling and vasoreactivity","volume":"77","author":"Houde","year":"2016","journal-title":"Adv Pharmacol"},{"key":"10.1016\/j.drudis.2026.104815_b0110","doi-asserted-by":"crossref","first-page":"2434","DOI":"10.1161\/01.CIR.102.19.2434","article-title":"Endothelins and endothelin receptor antagonists","volume":"102","author":"L\u00fcscher","year":"2000","journal-title":"Circulation"},{"key":"10.1016\/j.drudis.2026.104815_b0115","doi-asserted-by":"crossref","first-page":"9352","DOI":"10.3390\/ijms24119352","article-title":"Hyperglycemia and oxidative stress: an integral, updated and critical overview of their metabolic interconnections","volume":"24","author":"Gonz\u00e1lez","year":"2023","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.drudis.2026.104815_b0120","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.exer.2007.06.013","article-title":"Pro-inflammatory cytokines increase reactive oxygen species through mitochondria and NADPH oxidase in cultured RPE cells","volume":"85","author":"Yang","year":"2007","journal-title":"Exp Eye Res"},{"key":"10.1016\/j.drudis.2026.104815_b0125","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.2337\/db10-1281","article-title":"Endothelin-1 reduces glucose uptake in human skeletal muscle in vivo and in vitro","volume":"60","author":"Shemyakin","year":"2011","journal-title":"Diabetes"},{"key":"10.1016\/j.drudis.2026.104815_b0130","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/s41569-019-0176-3","article-title":"Endothelins in cardiovascular biology and therapeutics","volume":"16","author":"Dhaun","year":"2019","journal-title":"Nat Rev Cardiol"},{"key":"10.1016\/j.drudis.2026.104815_b0135","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s43152-024-00056-3","article-title":"Cellular and molecular mechanisms of insulin resistance","volume":"5","author":"Chandrasekaran","year":"2024","journal-title":"Curr Tissue Microenviron Rep"},{"key":"10.1016\/j.drudis.2026.104815_b0140","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1139\/cjpp-2019-0666","article-title":"Loss of endothelin type B receptor function improves insulin sensitivity in rats","volume":"98","author":"Rivera-Gonzalez","year":"2020","journal-title":"Can J Physiol Pharmacol"},{"key":"10.1016\/j.drudis.2026.104815_b0145","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1016\/j.bbadis.2015.06.026","article-title":"Synergistic induction of insulin resistance by endothelin-1 and cAMP in 3T3-L1 adipocytes","volume":"1852","author":"Chai","year":"2015","journal-title":"Biochim Biophys Acta"},{"key":"10.1016\/j.drudis.2026.104815_b0150","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.2337\/diabetes.52.8.1904","article-title":"Chronic endothelin-1 treatment leads to insulin resistance in vivo","volume":"52","author":"Wilkes","year":"2003","journal-title":"Diabetes"},{"key":"10.1016\/j.drudis.2026.104815_b0155","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1161\/CIRCULATIONAHA.105.563213","article-title":"Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms","volume":"113","author":"Kim","year":"2006","journal-title":"Circulation"},{"key":"10.1016\/j.drudis.2026.104815_b0160","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s11154-012-9229-1","article-title":"Role of insulin resistance in endothelial dysfunction","volume":"14","author":"Muniyappa","year":"2013","journal-title":"Rev Endocr Metab Disord"},{"key":"10.1016\/j.drudis.2026.104815_b0165","doi-asserted-by":"crossref","DOI":"10.14814\/phy2.12895","article-title":"Hyperinsulinemia augments endothelin-1 protein expression and impairs vasodilation of human skeletal muscle arterioles","volume":"4","author":"Mahmoud","year":"2016","journal-title":"Physiol Rep"},{"key":"10.1016\/j.drudis.2026.104815_b0170","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1007\/s12265-014-9545-9","article-title":"Impact of diabetes mellitus on the clinical response to cardiac resynchronization therapy in elderly people","volume":"7","author":"Sardu","year":"2014","journal-title":"J Cardiovasc Transl Res"},{"key":"10.1016\/j.drudis.2026.104815_b0175","doi-asserted-by":"crossref","DOI":"10.1016\/j.ajpc.2025.101349","article-title":"Endothelial dysfunction and cardiovascular outcomes in pre-menopausal women with high vs low breast fat accumulation: the role of TSP-1","volume":"24","author":"Sardu","year":"2025","journal-title":"Am J Prev Cardiol"},{"key":"10.1016\/j.drudis.2026.104815_b0180","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.3390\/ijms24021510","article-title":"Endothelial dysfunction drives CRTd outcome at 1-year follow-up: a novel role as biomarker for miR-130a-5p","volume":"24","author":"Sardu","year":"2023","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.drudis.2026.104815_b0185","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.2147\/VHRM.S3920","article-title":"The importance of endothelin-1 for microvascular dysfunction in diabetes","volume":"4","author":"Kalani","year":"2008","journal-title":"Vasc Health Risk Manag"},{"key":"10.1016\/j.drudis.2026.104815_b0190","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/nep.14130","article-title":"Endothelin receptor antagonists in kidney protection for diabetic kidney disease and beyond?","volume":"28","author":"Chung","year":"2023","journal-title":"Nephrology (Carlton)"},{"key":"10.1016\/j.drudis.2026.104815_b0195","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1006\/bbrc.1997.7394","article-title":"Angiotensin II increases vascular and renal endothelin-1 and functional endothelin converting enzyme activity in vivo: role of ETA receptors for endothelin regulation","volume":"238","author":"Barton","year":"1997","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.drudis.2026.104815_b0200","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1291\/hypres.27.433","article-title":"Dual effects of endothelin-1 (1-31): induction of mesangial cell migration and facilitation of monocyte recruitment through monocyte chemoattractant protein-1 production by mesangial cells","volume":"27","author":"Ishizawa","year":"2004","journal-title":"Hypertens Res"},{"key":"10.1016\/j.drudis.2026.104815_b0205","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/S1607-551X(09)70325-0","article-title":"Effects of specific endothelin-1 receptor antagonists on proliferation and fibronectin production of glomerular mesangial cells stimulated with Angiotensin II","volume":"22","author":"Kuo","year":"2006","journal-title":"Kaohsiung J Med Sci"},{"key":"10.1016\/j.drudis.2026.104815_b0210","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.semnephrol.2015.03.003","article-title":"ET and diabetic nephropathy: preclinical and clinical studies","volume":"35","author":"Gagliardini","year":"2015","journal-title":"Semin Nephrol"},{"key":"10.1016\/j.drudis.2026.104815_b0215","article-title":"Endothelin-1 is associated with fibrosis in proliferative diabetic retinopathy membranes","volume":"13","author":"Chang","year":"2018","journal-title":"PLoS One"},{"key":"10.1016\/j.drudis.2026.104815_b0220","doi-asserted-by":"crossref","first-page":"243","DOI":"10.2174\/1570161033476600","article-title":"Role of endothelin in diabetic retinopathy","volume":"1","author":"Lam","year":"2003","journal-title":"Curr Vasc Pharmacol"},{"key":"10.1016\/j.drudis.2026.104815_b0225","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1038\/eye.2017.74","article-title":"Aqueous humor endothelin-1 and total retinal blood flow in patients with non-proliferative diabetic retinopathy","volume":"31","author":"Khuu","year":"2017","journal-title":"Eye (Lond)"},{"key":"10.1016\/j.drudis.2026.104815_b0230","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.cyto.2009.11.004","article-title":"Roles of endothelin-1 and selected proinflammatory cytokines in the pathogenesis of proliferative diabetic retinopathy: analysis of vitreous samples","volume":"49","author":"Adamiec-Mroczek","year":"2010","journal-title":"Cytokine"},{"key":"10.1016\/j.drudis.2026.104815_b0235","doi-asserted-by":"crossref","first-page":"E683","DOI":"10.1210\/jc.2012-4119","article-title":"Elevated endothelin-1 (ET-1) levels may contribute to hypoadiponectinemia in childhood obesity","volume":"98","author":"Nacci","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.drudis.2026.104815_b0240","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1139\/cjpp-2019-0651","article-title":"Intricacies of the endothelin system in human obesity: role in the development of complications and potential as a therapeutic target","volume":"98","author":"Schinzari","year":"2020","journal-title":"Can J Physiol Pharmacol"},{"key":"10.1016\/j.drudis.2026.104815_b0245","doi-asserted-by":"crossref","first-page":"E1146","DOI":"10.1152\/ajpendo.00481.2004","article-title":"Endothelin-1 induces lipolysis in 3T3-L1 adipocytes","volume":"288","author":"Juan","year":"2005","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"10.1016\/j.drudis.2026.104815_b0250","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/ijo.2008.212","article-title":"Endothelin-1 stimulates human adipocyte lipolysis through the ET A receptor","volume":"33","author":"Eriksson","year":"2009","journal-title":"Int J Obes (Lond)"},{"key":"10.1016\/j.drudis.2026.104815_b0255","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/0163-7258(95)02015-2","article-title":"Endothelin receptor subtypes and their role in transmembrane signaling mechanisms","volume":"68","author":"Sokolovsky","year":"1995","journal-title":"Pharmacol Ther"},{"key":"10.1016\/j.drudis.2026.104815_b0260","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1210\/en.2006-0654","article-title":"Endothelin-1 regulates adiponectin gene expression and secretion in 3T3-L1 adipocytes via distinct signaling pathways","volume":"148","author":"Juan","year":"2007","journal-title":"Endocrinology"},{"key":"10.1016\/j.drudis.2026.104815_b0265","doi-asserted-by":"crossref","DOI":"10.1111\/apha.14214","article-title":"Adipocyte endothelin B receptor activation inhibits adiponectin production and causes insulin resistance in obese mice","volume":"240","author":"Rivera-Gonzalez","year":"2024","journal-title":"Acta Physiol (Oxf)"},{"key":"10.1016\/j.drudis.2026.104815_b0270","doi-asserted-by":"crossref","first-page":"3605","DOI":"10.1242\/jcs.01207","article-title":"Inhibition of adipocyte differentiation by mechanical stretching through ERK-mediated downregulation of PPARgamma2","volume":"117","author":"Tanabe","year":"2004","journal-title":"J Cell Sci"},{"key":"10.1016\/j.drudis.2026.104815_b0275","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.coph.2010.08.002","article-title":"Mechanisms of adiponectin regulation and use as a pharmacological target","volume":"10","author":"Phillips","year":"2010","journal-title":"Curr Opin Pharmacol"},{"key":"10.1016\/j.drudis.2026.104815_b0280","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1161\/CIRCRESAHA.113.301074","article-title":"Induction of vascular insulin resistance and endothelin-1 expression and acceleration of atherosclerosis by the overexpression of protein kinase C-\u03b2 isoform in the endothelium","volume":"113","author":"Li","year":"2013","journal-title":"Circ Res"},{"key":"10.1016\/j.drudis.2026.104815_b0285","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.bcp.2009.04.029","article-title":"Inflammatory cytokines in vascular dysfunction and vascular disease","volume":"78","author":"Sprague","year":"2009","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.drudis.2026.104815_b0290","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.2337\/diabetes.49.9.1561","article-title":"Endothelin 1 transcription is controlled by nuclear factor-kappaB in AGE-stimulated cultured endothelial cells","volume":"49","author":"Quehenberger","year":"2000","journal-title":"Diabetes"},{"key":"10.1016\/j.drudis.2026.104815_b0295","first-page":"604","article-title":"Disproportionately elevated proinsulin levels reflect the degree of impaired B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus","volume":"83","author":"R\u00f8der","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.drudis.2026.104815_b0300","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.1210\/jc.2004-0395","article-title":"Adipose tissue as an endocrine organ","volume":"89","author":"Kershaw","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.drudis.2026.104815_b0305","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1096\/fasebj.13.10.1231","article-title":"Leptin induces oxidative stress in human endothelial cells","volume":"13","author":"Bouloumie","year":"1999","journal-title":"FASEB J"},{"key":"10.1016\/j.drudis.2026.104815_b0310","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1161\/01.CIR.0000084503.91330.49","article-title":"Resistin promotes endothelial cell activation: further evidence of adipokine-endothelial interaction","volume":"108","author":"Verma","year":"2003","journal-title":"Circulation"},{"key":"10.1016\/j.drudis.2026.104815_b0315","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1161\/01.ATV.0000099786.99623.EF","article-title":"Adiponectin and metabolic syndrome","volume":"24","author":"Matsuzawa","year":"2004","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"10.1016\/j.drudis.2026.104815_b0320","doi-asserted-by":"crossref","DOI":"10.4061\/2011\/281240","article-title":"Vascular inflammation and endothelial dysfunction in experimental hypertension","volume":"2011","author":"Savoia","year":"2011","journal-title":"Int J Hypertens"},{"key":"10.1016\/j.drudis.2026.104815_b0325","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1053\/j.ackd.2019.03.001","article-title":"Inflammation, immunity, and oxidative stress in hypertension-partners in crime?","volume":"26","author":"Barrows","year":"2019","journal-title":"Adv Chronic Kidney Dis"},{"key":"10.1016\/j.drudis.2026.104815_b0330","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1007\/s003950050170","article-title":"Endothelin-1 induces interleukin-6 release via activation of the transcription factor NF-kappaB in human vascular smooth muscle cells","volume":"95","author":"Browatzki","year":"2000","journal-title":"Basic Res Cardiol"},{"key":"10.1016\/j.drudis.2026.104815_b0335","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/j.cell.2014.05.012","article-title":"Increased adipocyte O2 consumption triggers HIF-1\u03b1, causing inflammation and insulin resistance in obesity","volume":"157","author":"Lee","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.drudis.2026.104815_b0340","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1017\/S0029665109990206","article-title":"Cellular hypoxia and adipose tissue dysfunction in obesity","volume":"68","author":"Wood","year":"2009","journal-title":"Proc Nutr Soc"},{"key":"10.1016\/j.drudis.2026.104815_b0345","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/s41392-023-01652-9","article-title":"Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets","volume":"8","author":"Zhao","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"10.1016\/j.drudis.2026.104815_b0350","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1016\/j.cell.2024.03.034","article-title":"Gut symbionts alleviate MASH through a secondary bile acid biosynthetic pathway","volume":"187","author":"Nie","year":"2024","journal-title":"Cell"},{"key":"10.1016\/j.drudis.2026.104815_b0355","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1002\/hep.23280","article-title":"Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications","volume":"51","author":"Fabbrini","year":"2010","journal-title":"Hepatology"},{"key":"10.1016\/j.drudis.2026.104815_b0360","doi-asserted-by":"crossref","first-page":"523","DOI":"10.36740\/WLek201904103","article-title":"The role of endothelial dysfunction in the progression mechanisms of non-alcoholic steatohepatitis in patients with obesity and chronic kidney disease","volume":"72","author":"Khukhlina","year":"2019","journal-title":"Wiad Lek"},{"key":"10.1016\/j.drudis.2026.104815_b0365","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.3390\/cells11162511","article-title":"Endothelial cell dysfunction and nonalcoholic fatty liver disease (NAFLD): a concise review","volume":"11","author":"Nasiri-Ansari","year":"2022","journal-title":"Cells"},{"key":"10.1016\/j.drudis.2026.104815_b0370","doi-asserted-by":"crossref","first-page":"2622","DOI":"10.1007\/s10620-006-9147-8","article-title":"The serum endothelin-1 level in steatosis and NASH, and its relation with severity of liver fibrosis","volume":"52","author":"Degertekin","year":"2007","journal-title":"Dig Dis Sci"},{"key":"10.1016\/j.drudis.2026.104815_b0375","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1038\/labinvest.2015.95","article-title":"Pivotal role of liver sinusoidal endothelial cells in NAFLD\/NASH progression","volume":"95","author":"Miyao","year":"2015","journal-title":"Lab Invest"},{"key":"10.1016\/j.drudis.2026.104815_b0380","doi-asserted-by":"crossref","first-page":"400","DOI":"10.21037\/atm.2020.02.184","article-title":"The cellular pathways of liver fibrosis in non-alcoholic steatohepatitis","volume":"8","author":"M\u00e9ndez-S\u00e1nchez","year":"2020","journal-title":"Ann Transl Med"},{"key":"10.1016\/j.drudis.2026.104815_b0385","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.3390\/genes12111813","article-title":"Circulatory endothelin 1-regulating RNAs panel: promising biomarkers for non-invasive NAFLD\/NASH diagnosis and stratification: clinical and molecular pilot study","volume":"12","author":"Albadawy","year":"2021","journal-title":"Genes (Basel)"},{"key":"10.1016\/j.drudis.2026.104815_b0390","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1007\/s00018-023-04966-7","article-title":"Liver endothelial cells in NAFLD and transition to NASH and HCC","volume":"80","author":"Velliou","year":"2023","journal-title":"Cell Mol Life Sci"},{"key":"10.1016\/j.drudis.2026.104815_b0395","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1186\/s13046-019-1495-2","article-title":"Metformin in colorectal cancer: molecular mechanism, preclinical and clinical aspects","volume":"38","author":"Kamarudin","year":"2019","journal-title":"J Exp Clin Cancer Res"},{"key":"10.1016\/j.drudis.2026.104815_b0400","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.3892\/ol.2015.2883","article-title":"Effect of metformin on insulin-resistant endothelial cell function","volume":"9","author":"Chen","year":"2015","journal-title":"Oncol Lett"},{"key":"10.1016\/j.drudis.2026.104815_b0405","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.pharmthera.2018.07.007","article-title":"Endothelial function and dysfunction: Impact of metformin","volume":"192","author":"Nafisa","year":"2018","journal-title":"Pharmacol Ther"},{"key":"10.1016\/j.drudis.2026.104815_b0410","doi-asserted-by":"crossref","first-page":"9376","DOI":"10.7150\/thno.64706","article-title":"Metformin in cardiovascular diabetology: a focused review of its impact on endothelial function","volume":"11","author":"Ding","year":"2021","journal-title":"Theranostics"},{"key":"10.1016\/j.drudis.2026.104815_b0415","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.metabol.2006.10.010","article-title":"Metformin reduces endothelial cell expression of both the receptor for advanced glycation end products and lectin-like oxidized receptor 1","volume":"56","author":"Ouslimani","year":"2007","journal-title":"Metabolism"},{"key":"10.1016\/j.drudis.2026.104815_b0420","doi-asserted-by":"crossref","DOI":"10.1016\/j.vph.2019.106613","article-title":"Metformin inhibited homocysteine-induced upregulation of endothelin receptors through the Sirt1\/NF-\u03baB signaling pathway in vascular smooth muscle cells","volume":"124","author":"Chen","year":"2020","journal-title":"Vascul Pharmacol"},{"key":"10.1016\/j.drudis.2026.104815_b0425","article-title":"Metformin monotherapy with and without lifestyle changes affects anthropometric parameters, blood pressure, blood glucose, and lipid profile in Indian patients with newly diagnosed type 2 diabetes","volume":"16","author":"Sen","year":"2024","journal-title":"Cureus"},{"key":"10.1016\/j.drudis.2026.104815_b0430","article-title":"Metformin protects cardiovascular health in people with diabetes","volume":"9","author":"Chen","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"10.1016\/j.drudis.2026.104815_b0435","doi-asserted-by":"crossref","DOI":"10.1177\/20420188231222367","article-title":"Anti-inflammatory role of glucagon-like peptide 1 receptor agonists and its clinical implications","volume":"15","author":"Alharbi","year":"2024","journal-title":"Ther Adv Endocrinol Metab"},{"key":"10.1016\/j.drudis.2026.104815_b0440","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/s41392-024-01931-z","article-title":"Glucagon-like peptide-1 receptor: mechanisms and advances in therapy","volume":"9","author":"Zheng","year":"2024","journal-title":"Signal Transduct Target Ther"},{"key":"10.1016\/j.drudis.2026.104815_b0445","article-title":"Glucagon-like peptide-1 receptor agonists: new strategies and therapeutic targets to treat atherosclerotic cardiovascular disease","volume":"15","author":"Wang","year":"2024","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.drudis.2026.104815_b0450","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u03baB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct Target Ther"},{"key":"10.1016\/j.drudis.2026.104815_b0455","doi-asserted-by":"crossref","first-page":"331","DOI":"10.2174\/1573399812666150918150608","article-title":"Does glucagon-like peptide-1 ameliorate oxidative stress in diabetes? Evidence based on experimental and clinical studies","volume":"12","author":"Petersen","year":"2016","journal-title":"Curr Diabetes Rev"},{"key":"10.1016\/j.drudis.2026.104815_b0460","doi-asserted-by":"crossref","first-page":"202","DOI":"10.2174\/1570161112666140226122054","article-title":"Endothelin-1 signaling in vascular physiology and pathophysiology","volume":"12","author":"Sandoval","year":"2014","journal-title":"Curr Vasc Pharmacol"},{"key":"10.1016\/j.drudis.2026.104815_b0465","doi-asserted-by":"crossref","DOI":"10.1016\/j.molmet.2020.101102","article-title":"GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art","volume":"46","author":"Nauck","year":"2021","journal-title":"Mol Metab"},{"key":"10.1016\/j.drudis.2026.104815_b0470","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2337\/db15-0122","article-title":"Glucose-dependent insulinotropic polypeptide stimulates osteopontin expression in the vasculature via endothelin-1 and CREB","volume":"65","author":"Berglund","year":"2015","journal-title":"Diabetes"},{"key":"10.1016\/j.drudis.2026.104815_b0475","doi-asserted-by":"crossref","first-page":"H689","DOI":"10.1152\/ajpheart.00206.2011","article-title":"Enhanced endothelin-1 system activity with overweight and obesity","volume":"301","author":"Weil","year":"2011","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"10.1016\/j.drudis.2026.104815_b0480","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1056\/NEJMoa2206038","article-title":"Tirzepatide once weekly for the treatment of obesity","volume":"387","author":"Jastreboff","year":"2022","journal-title":"N Engl J Med"},{"key":"10.1016\/j.drudis.2026.104815_b0485","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.3892\/ijmm.2016.2578","article-title":"Sitagliptin inhibits endothelin-1 expression in the aortic endothelium of rats with streptozotocin-induced diabetes by suppressing the nuclear factor-\u03baB\/I\u03baB\u03b1 system through the activation of AMP-activated protein kinase","volume":"37","author":"Tang","year":"2016","journal-title":"Int J Mol Med"},{"key":"10.1016\/j.drudis.2026.104815_b0490","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.3389\/fimmu.2019.01050","article-title":"DPP-4 inhibitors as potential candidates for antihypertensive therapy: improving vascular inflammation and assisting the action of traditional antihypertensive drugs","volume":"10","author":"Zhang","year":"2019","journal-title":"Front Immunol"},{"key":"10.1016\/j.drudis.2026.104815_b0495","doi-asserted-by":"crossref","first-page":"C972","DOI":"10.1152\/ajpcell.00246.2023","article-title":"Effects of dipeptidyl peptidase 4 inhibition on the endothelial control of the vascular tone","volume":"325","author":"Ribeiro-Silva","year":"2023","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.1016\/j.drudis.2026.104815_b0500","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1161\/CIRCULATIONAHA.117.028136","article-title":"Cardiovascular actions and clinical outcomes with glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors","volume":"136","author":"Nauck","year":"2017","journal-title":"Circulation"},{"key":"10.1016\/j.drudis.2026.104815_b0505","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1253\/circj.CJ-12-1168","article-title":"Dipeptidyl peptidase-4 inhibitor, sitagliptin, improves endothelial dysfunction in association with its anti-inflammatory effects in patients with coronary artery disease and uncontrolled diabetes","volume":"77","author":"Matsubara","year":"2013","journal-title":"Circ J"},{"key":"10.1016\/j.drudis.2026.104815_b0510","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1016\/j.biopha.2018.09.148","article-title":"Vildagliptin protects endothelial cells against high glucose-induced damage","volume":"108","author":"Zhang","year":"2018","journal-title":"Biomed Pharmacother"},{"key":"10.1016\/j.drudis.2026.104815_b0515","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1056\/NEJMoa2024816","article-title":"Dapagliflozin in patients with chronic kidney disease","volume":"383","author":"Heerspink","year":"2020","journal-title":"N Engl J Med"},{"key":"10.1016\/j.drudis.2026.104815_b0520","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0140-6736(18)32590-X","article-title":"SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials","volume":"393","author":"Zelniker","year":"2019","journal-title":"Lancet"},{"key":"10.1016\/j.drudis.2026.104815_b0525","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.jacbts.2020.02.004","article-title":"Mechanisms of cardiovascular benefits of sodium glucose co-transporter 2 (SGLT2) inhibitors: a state-of-the-art review","volume":"5","author":"Lopaschuk","year":"2020","journal-title":"JACC Basic Transl Sci"},{"key":"10.1016\/j.drudis.2026.104815_b0530","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2021.112515","article-title":"Empagliflozin reduces oxidative stress through inhibition of the novel inflammation\/NHE\/[Na(+)](c)\/ROS-pathway in human endothelial cells","volume":"146","author":"Uthman","year":"2022","journal-title":"Biomed Pharmacother"},{"key":"10.1016\/j.drudis.2026.104815_b0535","doi-asserted-by":"crossref","first-page":"8189","DOI":"10.3390\/ijms21218189","article-title":"Empagliflozin inhibits basal and IL-1\u03b2-mediated MCP-1\/CCL2 and endothelin-1 expression in human proximal tubular cells","volume":"21","author":"Pirklbauer","year":"2020","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.drudis.2026.104815_b0540","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1007\/s13300-020-00885-z","article-title":"Effect of sodium-glucose cotransporter-2 inhibitors on endothelial function: a systematic review of preclinical studies","volume":"11","author":"Alshnbari","year":"2020","journal-title":"Diabetes Ther"},{"key":"10.1016\/j.drudis.2026.104815_b0545","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1161\/CIRCULATIONAHA.116.021887","article-title":"Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus","volume":"134","author":"Heerspink","year":"2016","journal-title":"Circulation"},{"key":"10.1016\/j.drudis.2026.104815_b0550","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1007\/s00125-018-4670-7","article-title":"SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review","volume":"61","author":"Verma","year":"2018","journal-title":"Diabetologia"},{"key":"10.1016\/j.drudis.2026.104815_b0555","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1161\/CIRCULATIONAHA.119.042375","article-title":"Effect of empagliflozin on left ventricular mass in patients with type 2 diabetes mellitus and coronary artery disease: the EMPA-HEART CardioLink-6 Randomized Clinical Trial","volume":"140","author":"Verma","year":"2019","journal-title":"Circulation"},{"key":"10.1016\/j.drudis.2026.104815_b0560","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s12933-017-0621-8","article-title":"Dapagliflozin acutely improves endothelial dysfunction, reduces aortic stiffness and renal resistive index in type 2 diabetic patients: a pilot study","volume":"16","author":"Solini","year":"2017","journal-title":"Cardiovasc Diabetol"},{"key":"10.1016\/j.drudis.2026.104815_b0565","doi-asserted-by":"crossref","DOI":"10.1016\/j.diabres.2025.112452","article-title":"Effects of combination therapy with SGLT2 inhibitors and GLP-1 receptor agonists on CRT response and clinical outcomes in in type 2 diabetes mellitus patients receiving chronic anti-diabetic medications: a multicenter observational study","volume":"228","author":"Sardu","year":"2025","journal-title":"Diabetes Res Clin Pract"},{"key":"10.1016\/j.drudis.2026.104815_b0570","doi-asserted-by":"crossref","first-page":"297","DOI":"10.2147\/VHRM.S993","article-title":"Peroxisome proliferator-activated receptor-gamma agonists and diabetes: current evidence and future perspectives","volume":"4","author":"Chiarelli","year":"2008","journal-title":"Vasc Health Risk Manag"},{"key":"10.1016\/j.drudis.2026.104815_b0575","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s11892-019-1270-y","article-title":"Thiazolidinediones: the forgotten diabetes medications","volume":"19","author":"Lebovitz","year":"2019","journal-title":"Curr Diab Rep"},{"key":"10.1016\/j.drudis.2026.104815_b0580","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.cell.2005.11.026","article-title":"The many faces of PPARgamma","volume":"123","author":"Lehrke","year":"2005","journal-title":"Cell"},{"key":"10.1016\/j.drudis.2026.104815_b0585","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0021-9150(01)00430-0","article-title":"Thiazolidinediones, peroxisome proliferator-activated receptor \u03b3 agonists, regulate endothelial cell growth and secretion of vasoactive peptides","volume":"158","author":"Fukunaga","year":"2001","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.drudis.2026.104815_b0590","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1161\/01.RES.0000127122.22685.0A","article-title":"Peroxisome proliferator-activated receptors and atherogenesis: regulators of gene expression in vascular cells","volume":"94","author":"Marx","year":"2004","journal-title":"Circ Res"},{"key":"10.1016\/j.drudis.2026.104815_b0595","doi-asserted-by":"crossref","first-page":"5512","DOI":"10.1111\/bph.13029","article-title":"The peroxisome proliferator-activated receptors in cardiovascular diseases: experimental benefits and clinical challenges","volume":"172","author":"Cheang","year":"2015","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.drudis.2026.104815_b0600","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":"10.1016\/j.drudis.2026.104815_b0605","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.2337\/diabetes.50.9.2094","article-title":"PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein","volume":"50","author":"Maeda","year":"2001","journal-title":"Diabetes"},{"key":"10.1016\/j.drudis.2026.104815_b0610","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.cmet.2014.08.005","article-title":"Thiazolidinediones and the promise of insulin sensitization in type 2 diabetes","volume":"20","author":"Soccio","year":"2014","journal-title":"Cell Metab"},{"key":"10.1016\/j.drudis.2026.104815_b0615","series-title":"Encyclopedia of Toxicology","first-page":"573","article-title":"Anti diabetic agents","author":"Ray","year":"2024"},{"key":"10.1016\/j.drudis.2026.104815_b0620","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1007\/s005990050027","article-title":"Early endothelial alterations in non-insulin-dependent diabetes mellitus","volume":"28","author":"Neri","year":"1998","journal-title":"Int J Clin Lab Res"},{"key":"10.1016\/j.drudis.2026.104815_b0625","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0026-0495(03)00212-9","article-title":"Benefits of gliclazide in the atherosclerotic process: decrease in monocyte adhesion to endothelial cells","volume":"52","author":"Renier","year":"2003","journal-title":"Metabolism"},{"key":"10.1016\/j.drudis.2026.104815_b0630","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ejphar.2012.02.006","article-title":"Differential effects of sulfonylurea derivatives on vascular ATP-sensitive potassium channels","volume":"681","author":"Engbersen","year":"2012","journal-title":"Eur J Pharmacol"},{"key":"10.1016\/j.drudis.2026.104815_b0635","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1161\/01.CIR.94.6.1276","article-title":"Chronic hyperglycemia impairs endothelial function and insulin sensitivity via different mechanisms in insulin-dependent diabetes mellitus","volume":"94","author":"M\u00e4kimattila","year":"1996","journal-title":"Circulation"},{"key":"10.1016\/j.drudis.2026.104815_b0640","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1517\/13543776.14.5.655","article-title":"Endothelin-converting enzyme inhibitors and their potential for cardiovascular and renal therapeutics","volume":"14","author":"Doggrell","year":"2004","journal-title":"Expert Opin Ther Pat"},{"key":"10.1016\/j.drudis.2026.104815_b0645","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1021\/jm990507o","article-title":"Potent and selective non-peptidic inhibitors of endothelin-converting enzyme-1 with sustained duration of action","volume":"43","author":"De Lombaert","year":"2000","journal-title":"J Med Chem"},{"key":"10.1016\/j.drudis.2026.104815_b0650","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2020.118223","article-title":"Endothelin converting enzyme-1 (ECE-1) deletion in association with Endothelin-1 downregulation ameliorates kidney fibrosis in mice","volume":"258","author":"Arfian","year":"2020","journal-title":"Life Sci"},{"key":"10.1016\/j.drudis.2026.104815_b0655","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1159\/000077132","article-title":"Increased expression of endothelin-converting enzyme-1c isoform in response to high glucose levels in endothelial cells","volume":"41","author":"Keynan","year":"2004","journal-title":"J Vasc Res"},{"key":"10.1016\/j.drudis.2026.104815_b0660","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1210\/en.2008-0524","article-title":"Role of protein kinase C in the expression of endothelin converting enzyme-1","volume":"150","author":"Khamaisi","year":"2009","journal-title":"Endocrinology"},{"key":"10.1016\/j.drudis.2026.104815_b0665","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1007\/s00424-013-1216-1","article-title":"Endothelin-converting enzyme-1 inhibition and renoprotection in end-stage renal disease","volume":"465","author":"Kuruppu","year":"2013","journal-title":"Pflugers Arch"},{"key":"10.1016\/j.drudis.2026.104815_b0670","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1172\/JCI7447","article-title":"Disruption of ECE-1 and ECE-2 reveals a role for endothelin-converting enzyme-2 in murine cardiac development","volume":"105","author":"Yanagisawa","year":"2000","journal-title":"J Clin Invest"},{"key":"10.1016\/j.drudis.2026.104815_b0675","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.jmb.2008.10.052","article-title":"Structure of human endothelin-converting enzyme I complexed with phosphoramidon","volume":"385","author":"Schulz","year":"2009","journal-title":"J Mol Biol"},{"key":"10.1016\/j.drudis.2026.104815_b0680","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/sj.bjp.0707398","article-title":"The peptidase inhibitor CGS-26303 increases endothelin converting enzyme-1 expression in endothelial cells through accumulation of big endothelin-1","volume":"152","author":"Raoch","year":"2007","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.drudis.2026.104815_b0685","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.ccm.2011.02.015","article-title":"Alternatives to lung transplantation: treatment of pulmonary arterial hypertension","volume":"32","author":"Corris","year":"2011","journal-title":"Clin Chest Med"},{"key":"10.1016\/j.drudis.2026.104815_b0690","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1007\/s11886-025-02262-3","article-title":"Endothelin receptor antagonists for the treatment of hypertension: recent data from clinical trials and implementation approach","volume":"27","author":"Manickavasagar","year":"2025","journal-title":"Curr Cardiol Rep"},{"key":"10.1016\/j.drudis.2026.104815_b0695","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1080\/17512433.2025.2532659","article-title":"Sparsentan: a dual endothelin and angiotensin II receptor antagonist approved for IgA nephropathy","volume":"18","author":"Colbert","year":"2025","journal-title":"Expert Rev Clin Pharmacol"},{"key":"10.1016\/j.drudis.2026.104815_b0700","doi-asserted-by":"crossref","first-page":"824","DOI":"10.3390\/jcm9030824","article-title":"Endothelin receptor antagonists: status quo and future perspectives for targeted therapy","volume":"9","author":"Enevoldsen","year":"2020","journal-title":"J Clin Med"},{"key":"10.1016\/j.drudis.2026.104815_b0705","doi-asserted-by":"crossref","first-page":"e0122","DOI":"10.1097\/MD.0000000000010122","article-title":"The safety of endothelin receptor antagonists in the treatment of pulmonary arterial hypertension: Protocol for a systemic review and network meta-analysis","volume":"97","author":"Gu","year":"2018","journal-title":"Medicine (Baltimore)"},{"key":"10.1016\/j.drudis.2026.104815_b0710","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1164\/rccm.201403-0446OC","article-title":"Bosentan in pulmonary hypertension associated with fibrotic idiopathic interstitial pneumonia","volume":"190","author":"Corte","year":"2014","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.drudis.2026.104815_b0715","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1056\/NEJMoa012212","article-title":"Bosentan therapy for pulmonary arterial hypertension","volume":"346","author":"Rubin","year":"2002","journal-title":"N Engl J Med"},{"key":"10.1016\/j.drudis.2026.104815_b0720","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1586\/14779072.3.6.985","article-title":"Sitaxsentan: a novel endothelin-A receptor antagonist for pulmonary arterial hypertension","volume":"3","author":"Widlitz","year":"2005","journal-title":"Expert Rev Cardiovasc Ther"},{"key":"10.1016\/j.drudis.2026.104815_b0725","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1177\/1753465812458014","article-title":"An update on the use of ambrisentan in pulmonary arterial hypertension","volume":"6","author":"D\u2019Alto","year":"2012","journal-title":"Ther Adv Respir Dis"},{"key":"10.1016\/j.drudis.2026.104815_b0730","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1161\/CIRCULATIONAHA.107.742510","article-title":"Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2","volume":"117","author":"Gali\u00e8","year":"2008","journal-title":"Circulation"},{"key":"10.1016\/j.drudis.2026.104815_b0735","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1056\/NEJMoa1213917","article-title":"Macitentan and morbidity and mortality in pulmonary arterial hypertension","volume":"369","author":"Pulido","year":"2013","journal-title":"N Engl J Med"},{"key":"10.1016\/j.drudis.2026.104815_b0740","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1186\/s12882-024-03713-9","article-title":"Safety and efficacy of sparsentan versus irbesartan in focal segmental glomerulosclerosis and IgA nephropathy: a systematic review and meta-analysis of randomized controlled trials","volume":"25","author":"Elnaga","year":"2024","journal-title":"BMC Nephrol"},{"key":"10.1016\/j.drudis.2026.104815_b0745","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1093\/ehjcvp\/pvae035","article-title":"After 30 years, the first endothelin-receptor antagonist (Aprocitentan) is approved for the treatment of arterial hypertension","volume":"10","author":"Tamargo","year":"2024","journal-title":"Eur Heart J Cardiovasc Pharmacother"},{"key":"10.1016\/j.drudis.2026.104815_b0750","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1139\/cjpp-2022-0010","article-title":"Aprocitentan and the endothelin system in resistant hypertension","volume":"100","author":"Clozel","year":"2022","journal-title":"Can J Physiol Pharmacol"},{"key":"10.1016\/j.drudis.2026.104815_b0755","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1124\/jpet.118.253864","article-title":"Pharmacological characterization of aprocitentan, a dual endothelin receptor antagonist, alone and in combination with blockers of the renin angiotensin system, in two models of experimental hypertension","volume":"368","author":"Trensz","year":"2019","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1016\/j.drudis.2026.104815_b0760","doi-asserted-by":"crossref","first-page":"i37","DOI":"10.1093\/ndt\/gfae214","article-title":"Selective endothelin A receptor antagonism in chronic kidney disease: improving clinical application","volume":"40","author":"Moedt","year":"2025","journal-title":"Nephrol Dial Transplant"}],"container-title":["Drug Discovery Today"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1359644626002205?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1359644626002205?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:02:36Z","timestamp":1791576156000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1359644626002205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,12]]},"references-count":152,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["S1359644626002205"],"URL":"https:\/\/doi.org\/10.1016\/j.drudis.2026.104815","relation":{},"ISSN":["1359-6446"],"issn-type":[{"value":"1359-6446","type":"print"}],"subject":[],"published":{"date-parts":[[2026,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The endothelin system: a potential target for the treatment of type 2 diabetes mellitus and associated cardiometabolic complications","name":"articletitle","label":"Article Title"},{"value":"Drug Discovery Today","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.drudis.2026.104815","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"104815"}}