{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T15:12:54Z","timestamp":1785510774718,"version":"3.56.0"},"reference-count":62,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2019,10,20]],"date-time":"2019-10-20T00:00:00Z","timestamp":1571529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Carvedilol (Cav), a nonselective \u03b2-blocker with \u03b11 adrenoceptor blocking effect, has been used as a standard therapy for coronary artery disease. This study investigated the effects of Cav on exosome expression and function, ATP-binding cassette transporter A1 (ABCA1) expression, and cholesterol efflux that are relevant to the process of atherosclerosis. Human monocytic (THP-1) cell line and human hepatic (Huh-7) cells were treated with Cav, and cholesterol efflux was measured. Exosomes from cell culture medium or mice serum were isolated using glycan-coated recognition beads. Low-density lipoprotein receptor knockout (ldlr\u2212\/\u2212) mice were fed with high-fat diet and treated with Cav. Cav accentuated cholesterol efflux and enhanced the expressions of ABCA1 protein and mRNA in both THP-1 and Huh-7 cells. In addition, Cav increased expression and function of exosomal ABCA1 in THP-1 macrophage exosomes. The mechanisms were associated with inhibition of nuclear factor-\u03baB (NF-\u03baB) and protein kinase B (Akt). In hypercholesterolemic ldlr\u2212\/\u2212 mice, Cav enhanced serum exosomal ABCA1 expression and suppressed atherosclerosis by inhibiting lipid deposition and macrophage accumulation. Cav halts atherosclerosis by enhancing cholesterol efflux and increasing ABCA1 expression in macrophages and in exosomes, possibly through NF-\u03baB and Akt signaling, which provides mechanistic insights regarding the beneficial effects of Cav on atherosclerotic cardiovascular disease.<\/jats:p>","DOI":"10.3390\/ijms20205202","type":"journal-article","created":{"date-parts":[[2019,10,21]],"date-time":"2019-10-21T03:40:29Z","timestamp":1571629229000},"page":"5202","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Carvedilol Ameliorates Experimental Atherosclerosis by Regulating Cholesterol Efflux and Exosome Functions"],"prefix":"10.3390","volume":"20","author":[{"given":"Sy-Jou","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan"},{"name":"Graduate Institute of Injury Prevention and Control, College of Public Health and Nutrition, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pi-Fen","family":"Tsui","sequence":"additional","affiliation":[{"name":"Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ping","family":"Chuang","sequence":"additional","affiliation":[{"name":"Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dapi Meng-Lin","family":"Chiang","sequence":"additional","affiliation":[{"name":"Biovesicle Inc., Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6759-0023","authenticated-orcid":false,"given":"Liv Weichien","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Ting","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Yen","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Cardiology and Cardiovascular Research Center, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Ming","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Hua","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Lin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Chien","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Graduate Institute of Physiology, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5167-8327","authenticated-orcid":false,"given":"Chin-Sheng","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1016\/j.jacc.2004.07.014","article-title":"ACC\/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction","volume":"44","author":"Antman","year":"2004","journal-title":"J. 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