{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T19:10:52Z","timestamp":1788117052907,"version":"build-2803163510"},"reference-count":99,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Science Council of Taiwan","award":["111-2314-B-038-028"],"award-info":[{"award-number":["111-2314-B-038-028"]}]},{"name":"the National Science Council of Taiwan","award":["112-2314-B-038-104-MY3"],"award-info":[{"award-number":["112-2314-B-038-104-MY3"]}]},{"name":"the National Science Council of Taiwan","award":["111TMU-SHH-01"],"award-info":[{"award-number":["111TMU-SHH-01"]}]},{"name":"the National Science Council of Taiwan","award":["112TMU-SHH-01"],"award-info":[{"award-number":["112TMU-SHH-01"]}]},{"name":"Ming-Yow Hung","award":["111-2314-B-038-028"],"award-info":[{"award-number":["111-2314-B-038-028"]}]},{"name":"Ming-Yow Hung","award":["112-2314-B-038-104-MY3"],"award-info":[{"award-number":["112-2314-B-038-104-MY3"]}]},{"name":"Ming-Yow Hung","award":["111TMU-SHH-01"],"award-info":[{"award-number":["111TMU-SHH-01"]}]},{"name":"Ming-Yow Hung","award":["112TMU-SHH-01"],"award-info":[{"award-number":["112TMU-SHH-01"]}]},{"name":"Taipei Medical University","award":["111-2314-B-038-028"],"award-info":[{"award-number":["111-2314-B-038-028"]}]},{"name":"Taipei Medical University","award":["112-2314-B-038-104-MY3"],"award-info":[{"award-number":["112-2314-B-038-104-MY3"]}]},{"name":"Taipei Medical University","award":["111TMU-SHH-01"],"award-info":[{"award-number":["111TMU-SHH-01"]}]},{"name":"Taipei Medical University","award":["112TMU-SHH-01"],"award-info":[{"award-number":["112TMU-SHH-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Lipoprotein(a) [Lp(a)]-induced inflammation contributes to coronary artery spasm (CAS) by the contraction of vascular smooth muscle cells. However, the interaction between Lp(a) and soluble CD36 (sCD36)\/interleukin (IL)-6\/RAS Homolog Family Member A (RhoA)-GTP signaling pathway has not been evaluated. Methods: We investigated the relevance of Lp(a)\/CD36 signaling in CAS patient monocyte-derived macrophages (PMDMs) and a human coronary artery smooth muscle cell (HCASMC) line using expression profile correlation analyses, molecular docking, RNA sequencing, flow cytometry, immunoblotting, and quantitative reverse transcription polymerase chain reaction. Results: Plasma Lp(a) and sCD36 levels in 41 CAS patients were significantly higher (p = 0.001) and positively correlated (r2 = 0.3145, p &lt; 0.001), a trend not observed in 36 non-CAS controls. RNA sequencing indicated a significant co-overexpression of CD36 and RhoA in Lp(a)-treated CAS PMDMs and HCASMCs, of which the mRNA and protein expression of CD36 and RhoA were significantly enhanced (p &lt; 0.001) dose-dependently. Lp(a) rather than LDL preferentially induced CD80+ PMDM (M1) polarization. In HCASMCs, the CD36 knockdown using either short hairpin RNA or natural biflavonoid amentoflavone suppressed Lp(a)-upregulated protein expression of CD36, RhoA-GTP, IL-6, tumor necrosis factor (TNF)-\u03b1, nuclear factor (NF)-\u03baB, and CD80; however, overexpressed CD36 increased their levels. Lp(a) decreased and amentoflavone increased the epigenetic expression of CD36 inhibitors, miR-335-5p, and miR-448, respectively. Reciprocally, an miRNA inhibitor or mimic could magnify or diminish Lp(a)-induced CD36, TNF-\u03b1, NF-\u03baB and IL-6 expressions in HCASMCs, respectively. Conclusions: Elevated Lp(a) levels upregulate the CD36-dependent TNF-\u03b1\/NF-\u03baB\/IL-6\/RhoA-GTP signaling pathway in CAS PMDMs and HCASMCs, indicating that Lp(a)\/CD36 inflammatory signaling, HCASMC activation, and macrophage M1 polarization mediate CAS development.<\/jats:p>","DOI":"10.3390\/ph18091384","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T14:31:41Z","timestamp":1758033101000},"page":"1384","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Lipoprotein(a)\/CD36 Interaction Drives IL-6\/RhoA-GTP Signaling and miRNA Epigenetic Regulation in Coronary Artery Spasm"],"prefix":"10.3390","volume":"18","author":[{"given":"Yen-Kuang","family":"Lin","sequence":"first","affiliation":[{"name":"Graduate Institute of Athletics and Coaching Science, National Taiwan Sport University, No. 250 Wenhua 1st Rd., Guishan, Taoyuan 33301, Taiwan"},{"name":"Biostatistics Research Center, Taipei Medical University, Taipei City 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2268-9246","authenticated-orcid":false,"given":"Tsung-Han","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Center for Management and Development, Taipei Medical University, Taipei City 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5189-9755","authenticated-orcid":false,"given":"Chi-Tai","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Medical Research and Education, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan"},{"name":"Continuing Education Program of Food Biotechnology Applications, College of Science and Engineering, National Taitung University, Taitung 95092, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2679-1205","authenticated-orcid":false,"given":"Vijesh Kumar","family":"Yadav","sequence":"additional","affiliation":[{"name":"Department of Medical Research and Education, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan"},{"name":"Continuing Education Program of Food Biotechnology Applications, College of Science and Engineering, National Taitung University, Taitung 95092, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8235-0877","authenticated-orcid":false,"given":"Iat-Hang","family":"Fong","sequence":"additional","affiliation":[{"name":"Department of Medical Research and Education, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan"},{"name":"Continuing Education Program of Food Biotechnology Applications, College of Science and Engineering, National Taitung University, Taitung 95092, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuang-Tai","family":"Kuo","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9751-6710","authenticated-orcid":false,"given":"Nicholas G.","family":"Kounis","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Patras Medical School, Rion, 26504 Patras, Achaia, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, University of California, Riverside, Riverside, CA 92521, USA"},{"name":"Department of Cardiology, Riverside Medical Clinic, Riverside, CA 92506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Yow","family":"Hung","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei City 11031, Taiwan"},{"name":"Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan"},{"name":"Taipei Heart Institute, Taipei Medical University, Taipei City 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Writing Committee Members, Gulati, M., Levy, P.D., Mukherjee, D., Amsterdam, E., Bhatt, D.L., Birtcher, K.K., Blankstein, R., Boyd, J., and Bullock-Palmer, R.P. (2022). 2021 AHA\/ACC\/ASE\/CHEST\/SAEM\/SCCT\/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines. J. Cardiovasc. Comput. Tomogr., 16, 54\u2013122.","DOI":"10.1016\/j.jcct.2021.11.009"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1016\/j.jacc.2015.02.060","article-title":"Increased Numbers of Coronary Events in Winter and Spring Due to Coronary Artery Spasm: Effect of Age, Sex, Smoking, and Inflammation","volume":"65","author":"Hung","year":"2015","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.amjcard.2003.11.033","article-title":"Comparison of peripheral monocyte counts in patients with and without coronary spasm and without fixed coronary narrowing","volume":"93","author":"Hung","year":"2004","journal-title":"Am. J. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Hung, M.-J., Hsu, K.-H., Hu, W.-S., Chang, N.-C., and Hung, M.-Y. (2013). C-reactive protein for predicting prognosis and its gender-specific associations with diabetes mellitus and hypertension in the development of coronary artery spasm. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077655"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1016\/j.amjcard.2005.12.035","article-title":"Comparison of serum levels of inflammatory markers in patients with coronary vasospasm without significant fixed coronary artery disease versus patients with stable angina pectoris and acute coronary syndromes with significant fixed coronary artery disease","volume":"97","author":"Hung","year":"2006","journal-title":"Am. J. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.freeradbiomed.2018.03.050","article-title":"Activation of the monocytic \u03b17 nicotinic acetylcholine receptor modulates oxidative stress and inflammation-associated development of coronary artery spasm via a p38 MAP-kinase signaling-dependent pathway","volume":"120","author":"Hung","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1161\/01.CIR.94.3.266","article-title":"Nitric oxide activity is deficient in spasm arteries of patients with coronary spastic angina","volume":"94","author":"Kugiyama","year":"1996","journal-title":"Circulation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1016\/S0735-1097(00)00550-7","article-title":"Lipoprotein(a) is a risk factor for occurrence of acute myocardial infarction in patients with coronary vasospasm","volume":"35","author":"Miwa","year":"2000","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.jacc.2013.08.1639","article-title":"New therapeutic targets for calcific aortic valve stenosis: The lipoprotein(a)-lipoprotein-associated phospholipase A2-oxidized phospholipid axis","volume":"63","author":"Hung","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1194\/jlr.M800174-JLR200","article-title":"A novel function of lipoprotein [a] as a preferential carrier of oxidized phospholipids in human plasma","volume":"49","author":"Bergmark","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9964689","DOI":"10.1155\/2022\/9964689","article-title":"Apolipoprotein (a)\/Lipoprotein(a)-Induced Oxidative-Inflammatory \u03b17-nAChR\/p38 MAPK\/IL-6\/RhoA-GTP Signaling Axis and M1 Macrophage Polarization Modulate Inflammation-Associated Development of Coronary Artery Spasm","volume":"2022","author":"Lin","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.atherosclerosis.2012.01.001","article-title":"Increased leukocyte Rho-associated coiled-coil containing protein kinase activity predicts the presence and severity of coronary vasospastic angina","volume":"221","author":"Hung","year":"2012","journal-title":"Atherosclerosis"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Pucha\u0142owicz, K., and Ra\u0107, M.E. (2020). The Multifunctionality of CD36 in Diabetes Mellitus and Its Complications-Update in Pathogenesis, Treatment and Monitoring. Cells, 9.","DOI":"10.3390\/cells9081877"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kaewmalee, J., Ontawong, A., Duangjai, A., Tansakul, C., Rukachaisirikul, V., Muanprasat, C., and Srimaroeng, C. (2021). High-Efficacy \u03b1,\u03b2-Dehydromonacolin S Improves Hepatic Steatosis and Suppresses Gluconeogenesis Pathway in High-Fat Diet-Induced Obese Rats. Pharmaceuticals, 14.","DOI":"10.3390\/ph14040375"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e24529","DOI":"10.1002\/jcla.24529","article-title":"Genetic variants, gene expression, and soluble CD36 analysis in acute coronary syndrome: Differential protein concentration between ST-segment elevation myocardial infarction and unstable angina","volume":"36","author":"Valle","year":"2022","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1161\/01.RES.0000016164.02525.B4","article-title":"CD36 mediates the cardiovascular action of growth hormone-releasing peptides in the heart","volume":"90","author":"Bodart","year":"2002","journal-title":"Circ. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.7150\/ijms.43472","article-title":"Myocardial Ischemic Syndromes, Heart Failure Syndromes, Electrocardiographic Abnormalities, Arrhythmic Syndromes and Angiographic Diagnosis of Coronary Artery Spasm: Literature Review","volume":"17","author":"Hung","year":"2020","journal-title":"Int. J. Med. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1001\/archinte.163.1.93","article-title":"C-reactive protein as a predictor for incident diabetes mellitus among middle-aged men: Results from the MONICA Augsburg cohort study, 1984\u20131998","volume":"163","author":"Thorand","year":"2003","journal-title":"Arch. Intern. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1093\/cvr\/cvx045","article-title":"Inhibition of sarcolemmal FAT\/CD36 by sulfo-N-succinimidyl oleate rapidly corrects metabolism and restores function in the diabetic heart following hypoxia\/reoxygenation","volume":"113","author":"Mansor","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.plefa.2012.04.009","article-title":"CD36 as a target to prevent cardiac lipotoxicity and insulin resistance","volume":"88","author":"Glatz","year":"2013","journal-title":"Prostagland. Leukot. Essent. Fat. Acids"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.3349\/ymj.2018.59.9.1057","article-title":"Impact of Insulin Resistance on Acetylcholine-Induced Coronary Artery Spasm in Non-Diabetic Patients","volume":"59","author":"Kang","year":"2018","journal-title":"Yonsei Med. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2630","DOI":"10.7150\/ijms.57987","article-title":"Association between Coronary Artery Spasm and the risk of incident Diabetes: A Nationwide population-based Cohort Study","volume":"18","author":"Hung","year":"2021","journal-title":"Int. J. Med. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3132\/dvdr.2009.003","article-title":"Circulating soluble CD36 is associated with glucose metabolism and interleukin-6 in glucose-intolerant men","volume":"6","author":"Handberg","year":"2009","journal-title":"Diab. Vasc. Dis. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1523\/JNEUROSCI.5205-07.2008","article-title":"Nuclear factor-kappaB activation and postischemic inflammation are suppressed in CD36-null mice after middle cerebral artery occlusion","volume":"28","author":"Kunz","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Tong, L., and Tergaonkar, V. (2014). Rho protein GTPases and their interactions with NF\u03baB: Crossroads of inflaowiojldflmmation and matrix biology. Biosci. Rep., 34.","DOI":"10.1042\/BSR20140021"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"H458","DOI":"10.1152\/ajpheart.00366.2020","article-title":"SIRT1-mediated deacetylation of NF-\u03baB inhibits the MLCK\/MLC2 pathway and the expression of ET-1, thus alleviating the development of coronary artery spasm","volume":"320","author":"Wu","year":"2021","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1128\/IAI.66.5.2365-2367.1998","article-title":"Lipoprotein(a) inhibits lipopolysaccharide-induced tumor necrosis factor alpha production by human mononuclear cells","volume":"66","author":"Netea","year":"1998","journal-title":"Infect. Immun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.freeradbiomed.2011.11.002","article-title":"Role of reactive oxygen and nitrogen species in the vascular responses to inflammation","volume":"52","author":"Kvietys","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Li, C., Ma, Q., Toan, S., Wang, J., Zhou, H., and Liang, J. (2020). SERCA overexpression reduces reperfusion-mediated cardiac microvascular damage through inhibition of the calcium\/MCU\/mPTP\/necroptosis signaling pathways. Redox Biol., 36.","DOI":"10.1016\/j.redox.2020.101659"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nri2922","article-title":"Immunometabolism: An emerging frontier","volume":"11","author":"Mathis","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e20211314","DOI":"10.1084\/jem.20211314","article-title":"CD36, a signaling receptor and fatty acid transporter that regulates immune cell metabolism and fate","volume":"219","author":"Chen","year":"2022","journal-title":"J. Exp. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1182\/blood.V87.5.2020.2020","article-title":"Regulated expression of CD36 during monocyte-to-macrophage differentiation: Potential role of CD36 in foam cell formation","volume":"87","author":"Huh","year":"1996","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S0092-8674(00)81575-5","article-title":"PPARgamma promotes monocyte\/macrophage differentiation and uptake of oxidized LDL","volume":"93","author":"Tontonoz","year":"1998","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1161\/01.ATV.16.8.1019","article-title":"Regulation of monocyte CD36 and thrombospondin-1 expression by soluble mediators","volume":"16","author":"Yesner","year":"1996","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1038\/nm1626","article-title":"Platelet CD36 links hyperlipidemia, oxidant stress and a prothrombotic phenotype","volume":"13","author":"Podrez","year":"2007","journal-title":"Nat. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.omtn.2022.12.009","article-title":"Positive feedback loop of miR-320 and CD36 regulates the hyperglycemic memory-induced diabetic diastolic cardiac dysfunction","volume":"31","author":"Zhan","year":"2022","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1161\/hy0202.103129","article-title":"Endothelin-1\u2013induced enhancement of coronary smooth muscle contraction via MAPK-dependent and MAPK-independent [Ca2+]i sensitization pathways","volume":"39","author":"Cain","year":"2002","journal-title":"Hypertension"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1042\/CS20110523","article-title":"Toll-like receptor 4 contributes to blood pressure regulation and vascular contraction in spontaneously hypertensive rats","volume":"122","author":"Bomfim","year":"2012","journal-title":"Clin. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e12","DOI":"10.15420\/ecr.2019.20","article-title":"Coronary Artery Spasm: The Interplay Between Endothelial Dysfunction and Vascular Smooth Muscle Cell Hyperreactivity","volume":"15","author":"Hubert","year":"2020","journal-title":"Eur. Cardiol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Baghdadi, A., Dunn, W.R., and Ralevic, V. (2025). Involvement of purinergic signalling in the vasomotor response to hypochlorous acid in porcine coronary artery. Purinergic Signal., Online ahead of print.","DOI":"10.1007\/s11302-025-10086-7"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.atherosclerosis.2014.01.049","article-title":"Lipoprotein(a): Fasting and nonfasting levels, inflammation, and cardiovascular risk","volume":"234","author":"Langsted","year":"2014","journal-title":"Atherosclerosis"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"38517","DOI":"10.1074\/jbc.M205924200","article-title":"A novel family of atherogenic oxidized phospholipids promotes macrophage foam cell formation via the scavenger receptor CD36 and is enriched in atherosclerotic lesions","volume":"277","author":"Podrez","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1111\/j.1365-2362.1993.tb00724.x","article-title":"Smoking and plasma lipoproteins in man: Effects on low density lipoprotein cholesterol levels and high density lipoprotein subfraction distribution","volume":"23","author":"Freeman","year":"1993","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1161\/CIRCULATIONAHA.107.715698","article-title":"Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population: The Copenhagen City Heart Study","volume":"117","author":"Kamstrup","year":"2008","journal-title":"Circulation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"480784","DOI":"10.1155\/2012\/480784","article-title":"A Systematic Literature Review of the Association of Lipoprotein(a) and Autoimmune Diseases and Atherosclerosis","volume":"2012","author":"Missala","year":"2012","journal-title":"Int. J. Rheumatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1097\/00042737-200112000-00004","article-title":"Increased levels of lipoprotein (a) in Crohn\u2019s disease: A relation to thrombosis?","volume":"13","author":"Koutroubakis","year":"2001","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1046\/j.1523-1755.1999.00273.x","article-title":"Inflammation enhances cardiovascular risk and mortality in hemodialysis patients","volume":"55","author":"Zimmermann","year":"1999","journal-title":"Kidney Int."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/0021-9150(89)90218-9","article-title":"Transient changes of serum lipoprotein(a) as an acute phase protein","volume":"78","author":"Maeda","year":"1989","journal-title":"Atherosclerosis"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1194\/jlr.R060582","article-title":"Lipoprotein (a): Truly a direct prothrombotic factor in cardiovascular disease?","volume":"57","author":"Boffa","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0014-5793(84)80473-1","article-title":"Kringles: Modules specialized for protein binding. Homology of the gelatin-binding region of fibronectin with the kringle structures of proteases","volume":"171","author":"Patthy","year":"1984","journal-title":"FEBS Lett."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.pathol.2018.11.003","article-title":"Lipoprotein(a) catabolism: A case of multiple receptors","volume":"51","author":"McCormick","year":"2019","journal-title":"Pathology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/370460a0","article-title":"Activation of transforming growth factor-beta is inhibited in transgenic apolipoprotein(a) mice","volume":"370","author":"Grainger","year":"1994","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1538\/expanim.23-0021","article-title":"Humanized CD36 (hCD36) mouse model supports the preclinical evaluation of therapeutic candidates targeting CD36","volume":"72","author":"Xie","year":"2023","journal-title":"Exp. Anim."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1007\/BF02535613","article-title":"Lipoprotein(a): Nonhuman primate models","volume":"26","author":"Makino","year":"1991","journal-title":"Lipids"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/jmp.12160","article-title":"Rhesus monkey (Macaca mulatta) lipoprotein(a) and apolipoprotein(a): High frequency of small size apolipoprotein(a) isoforms","volume":"44","author":"Enkhmaa","year":"2015","journal-title":"J. Med. Primatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e030651","DOI":"10.1136\/bmjopen-2019-030651","article-title":"Levels of Lipoprotein (a) in patients with coronary artery disease with and without inflammatory rheumatic disease: A cross-sectional study","volume":"9","author":"Holm","year":"2019","journal-title":"BMJ Open"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Berthold, H.K., Laudes, M., Krone, W., and Gouni-Berthold, I. (2011). Association between the interleukin-6 promoter polymorphism -174G\/C and serum lipoprotein(a) concentrations in humans. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024719"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1194\/jlr.P052209","article-title":"IL-6 blockade by monoclonal antibodies inhibits apolipoprotein (a) expression and lipoprotein (a) synthesis in humans","volume":"56","author":"Schulte","year":"2015","journal-title":"J. Lipid Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.2337\/dc10-0460","article-title":"Increased CD36 expression signals monocyte activation among patients with type 2 diabetes","volume":"33","author":"Sun","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1161\/ATVBAHA.118.312186","article-title":"CD36 Enhances Vascular Smooth Muscle Cell Proliferation and Development of Neointimal Hyperplasia","volume":"39","author":"Yue","year":"2019","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"263","DOI":"10.5551\/jat.10603","article-title":"Patients with CD36 deficiency are associated with enhanced atherosclerotic cardiovascular diseases","volume":"19","author":"Masuda","year":"2012","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Kilian, L.S., Voran, J., Frank, D., and Rangrez, A.Y. (2021). RhoA: A dubious molecule in cardiac pathophysiology. J. Biomed. Sci., 28.","DOI":"10.1186\/s12929-021-00730-w"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1016\/S0016-5085(03)00283-X","article-title":"Rho kinase blockade prevents inflammation via nuclear factor kappa B inhibition: Evidence in Crohn\u2019s disease and experimental colitis","volume":"124","author":"Segain","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1161\/CIRCRESAHA.115.306532","article-title":"RhoA\/Rho-Kinase in the Cardiovascular System","volume":"118","author":"Shimokawa","year":"2016","journal-title":"Circ. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.1096\/fj.03-0039fje","article-title":"Human muscle cells express a B7-related molecule, B7-H1, with strong negative immune regulatory potential: A novel mechanism of counterbalancing the immune attack in idiopathic inflammatory myopathies","volume":"17","author":"Wiendl","year":"2003","journal-title":"FASEB J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1161\/ATVBAHA.109.200758","article-title":"Human vascular smooth muscle cells lack essential costimulatory molecules to activate allogeneic memory T cells","volume":"30","author":"Zhang","year":"2010","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"834","DOI":"10.4049\/jimmunol.174.2.834","article-title":"Transcriptional profiling reveals complex regulation of the monocyte IL-1 beta system by IL-13","volume":"174","author":"Scotton","year":"2005","journal-title":"J. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1161\/CIRCRESAHA.119.315833","article-title":"Mitochondrial Metabolic Reprogramming by CD36 Signaling Drives Macrophage Inflammatory Responses","volume":"125","author":"Chen","year":"2019","journal-title":"Circ. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1038\/s41577-021-00529-8","article-title":"A guide to interrogating immunometabolism","volume":"21","author":"Voss","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/nrcardio.2014.173","article-title":"Macrophage subsets in atherosclerosis","volume":"12","author":"Colin","year":"2015","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1161\/CIRCULATIONAHA.116.020838","article-title":"Oxidized Phospholipids on Lipoprotein(a) Elicit Arterial Wall Inflammation and an Inflammatory Monocyte Response in Humans","volume":"134","author":"Bekkering","year":"2016","journal-title":"Circulation"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1161\/01.CIR.0000047279.42427.6D","article-title":"Nicotine strongly activates dendritic cell-mediated adaptive immunity: Potential role for progression of atherosclerotic lesions","volume":"107","author":"Aicher","year":"2003","journal-title":"Circulation"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.immuni.2005.10.001","article-title":"Macrophage polarization comes of age","volume":"23","author":"Mantovani","year":"2005","journal-title":"Immunity"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3523642","DOI":"10.1155\/2018\/3523642","article-title":"Involvement of M1 Macrophage Polarization in Endosomal Toll-Like Receptors Activated Psoriatic Inflammation","volume":"2018","author":"Lu","year":"2018","journal-title":"Mediat. Inflamm."},{"key":"ref_75","first-page":"161","article-title":"The Role of MicroRNAs in Human Diseases","volume":"2","author":"Ardekani","year":"2010","journal-title":"Avicenna. J. Med. Biotechnol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Park, C.S., Kim, I., Oh, G.C., Han, J.K., Yang, H.M., Park, K.W., Cho, H.J., Kang, H.J., Koo, B.K., and Chung, W.Y. (2020). Diagnostic Utility and Pathogenic Role of Circulating MicroRNAs in Vasospastic Angina. J. Clin. Med., 9.","DOI":"10.3390\/jcm9051313"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1007\/s13258-021-01150-8","article-title":"microRNA profiles of serum exosomes derived from children with nonalcoholic fatty liver","volume":"44","author":"Zhang","year":"2022","journal-title":"Genes Genom."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1097\/MCA.0000000000000144","article-title":"Pioglitazone, a peroxisome proliferator-activated receptor \u03b3 activator, suppresses coronary spasm","volume":"25","author":"Morita","year":"2014","journal-title":"Coron. Artery Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"101428","DOI":"10.1016\/j.molmet.2021.101428","article-title":"CD36 promotes de novo lipogenesis in hepatocytes through INSIG2-dependent SREBP1 processing","volume":"57","author":"Zeng","year":"2022","journal-title":"Mol. Metab."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Jiang, T., Zhang, G., and Lou, Z. (2020). Role of the Sterol Regulatory Element Binding Protein Pathway in Tumorigenesis. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.01788"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"22294","DOI":"10.1007\/s11356-017-9771-1","article-title":"MiR-448 promotes vascular smooth muscle cell proliferation and migration in through directly targeting MEF2C","volume":"24","author":"Zhang","year":"2017","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1111\/j.1365-2990.2011.01172.x","article-title":"The expression of CD36 in vessels with blood-brain barrier impairment in a stroke-prone hypertensive model","volume":"37","author":"Ueno","year":"2011","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1016\/j.jmb.2017.05.008","article-title":"miR-125a-5p Modulates Phenotypic Switch of Vascular Smooth Muscle Cells by Targeting ETS-1","volume":"429","author":"Gareri","year":"2017","journal-title":"J. Mol. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4000","DOI":"10.1210\/en.2013-1299","article-title":"MicroRNAs in cardiovascular health: From order to disorder","volume":"154","author":"Karunakaran","year":"2013","journal-title":"Endocrinology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1089\/nat.2020.0871","article-title":"Efficiency and Target Derepression of Anti-miR-92a: Results of a First in Human Study","volume":"30","author":"Abplanalp","year":"2020","journal-title":"Nucleic Acid. Ther."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1016\/j.jacbts.2023.09.006","article-title":"Development of a Mechanism-Based Next-Generation Therapeutic for Heart Failure Derived from the Dark Genome","volume":"8","author":"Viereck","year":"2023","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1152\/japplphysiol.00752.2003","article-title":"Involvement of p42\/44 MAPK and RhoA protein in augmentation of ACh-induced bronchial smooth muscle contraction by TNF-alpha in rats","volume":"97","author":"Sakai","year":"2004","journal-title":"J. Appl. Physiol. (1985)"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"115733","DOI":"10.1016\/j.taap.2021.115733","article-title":"Amentoflavone prevents ox-LDL-induced lipid accumulation by suppressing the PPAR\u03b3\/CD36 signal pathway","volume":"431","author":"Zhuang","year":"2021","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Xiong, X., Tang, N., Lai, X., Zhang, J., Wen, W., Li, X., Li, A., Wu, Y., and Liu, Z. (2021). Insights into Amentoflavone: A Natural Multifunctional Biflavonoid. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.768708"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Zhang, H., Ban, Y.M., Li, D.M., Wang, G., Gu, J., and Zhu, L. (2024). Amentoflavone for treating cardiocerebrovascular diseases and neurological disorders. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1406510"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"108296","DOI":"10.1016\/j.intimp.2021.108296","article-title":"Cardioprotective effects of Amentoflavone by suppression of apoptosis and inflammation on an in vitro and vivo model of myocardial ischemia-reperfusion injury","volume":"101","author":"Li","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"154922","DOI":"10.1016\/j.phymed.2023.154922","article-title":"Amentoflavone mitigates doxorubicin-induced cardiotoxicity by suppressing cardiomyocyte pyroptosis and inflammation through inhibition of the STING\/NLRP3 signalling pathway","volume":"117","author":"Fang","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Kim, G.L., Jang, E.H., Lee, D.E., Bang, C., Kang, H., Kim, S., Yoon, S.Y., Lee, D.H., Na, J.H., and Lee, S. (2020). Amentoflavone, active compound of Selaginella tamariscina, inhibits in vitro and in vivo TGF-\u03b2-induced metastasis of human cancer cells. Arch. Biochem. Biophys., 687.","DOI":"10.1016\/j.abb.2020.108384"},{"key":"ref_94","first-page":"963","article-title":"Amentoflavone induces cell-cycle arrest and apoptosis in MCF-7 human breast cancer cells via mitochondria-dependent pathway","volume":"26","author":"Pei","year":"2012","journal-title":"In Vivo"},{"key":"ref_95","first-page":"207","article-title":"Amentoflavone stimulates apoptosis in B16F-10 melanoma cells by regulating bcl-2, p53 as well as caspase-3 genes and regulates the nitric oxide as well as proinflammatory cytokine production in B16F-10 melanoma cells, tumor associated macrophages and peritoneal macrophages","volume":"7","author":"Guruvayoorappan","year":"2008","journal-title":"J. Exp. Ther. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.1161\/01.CIR.99.21.2829","article-title":"ACC\/AHA\/ACP-ASIM guidelines for the management of patients with chronic stable angina: Executive summary and recommendations. A Report of the American College of Cardiology\/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients with Chronic Stable Angina)","volume":"99","author":"Gibbons","year":"1999","journal-title":"Circulation"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"JCS Joint Working Group (2010). Guidelines for diagnosis and treatment of patients with vasospastic angina (coronary spastic angina) (JCS 2008): Digest version. Circ. J., 74, 1745\u20131762.","DOI":"10.1253\/circj.CJ-10-74-0802"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1016\/j.ehj.2004.06.026","article-title":"C-reactive protein levels determine systemic nitric oxide bioavailability in patients with coronary artery disease","volume":"25","author":"Fichtlscherer","year":"2004","journal-title":"Eur. Heart J."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"160","DOI":"10.4103\/1947-2714.128482","article-title":"Western blot: Technique, theory and trouble shooting","volume":"6","author":"Liu","year":"2014","journal-title":"N. Am. J. Med. Sci."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/9\/1384\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:46:35Z","timestamp":1760035595000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/9\/1384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,16]]},"references-count":99,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ph18091384"],"URL":"https:\/\/doi.org\/10.3390\/ph18091384","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,16]]}}}