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Yet, several recent pharmacological and genetic studies have failed to demonstrate that increased plasma levels of HDL-C resulted in decreased cardiovascular disease risk, giving rise to a controversy regarding whether plasma levels of HDL-C reflect HDL function, or that HDL is even as protective as assumed. The evidence from preclinical and (limited) clinical studies shows that HDL can promote the regression of atherosclerosis when the levels of functional particles are increased from endogenous or exogenous sources. The data show that regression results from a combination of reduced plaque lipid and macrophage contents, as well as from a reduction in its inflammatory state. Although more research will be needed regarding basic mechanisms and to establish that these changes translate clinically to reduced cardiovascular disease events, that HDL can regress plaques suggests that the recent trial failures do not eliminate HDL from consideration as an atheroprotective agent but rather emphasizes the important distinction between HDL function and plasma levels of HDL-C.<\/jats:p>","DOI":"10.1161\/circresaha.114.300760","type":"journal-article","created":{"date-parts":[[2014,1,2]],"date-time":"2014-01-02T21:23:35Z","timestamp":1388697815000},"page":"205-213","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":160,"title":["High-Density Lipoprotein and Atherosclerosis Regression"],"prefix":"10.1161","volume":"114","author":[{"given":"Jonathan E.","family":"Feig","sequence":"first","affiliation":[{"name":"From the Departments of Medicine (Cardiology) and Cell Biology, Marc and Ruti Bell Vascular Biology Program, New York University School of Medicine, New York, NY (J.E.F., B.H., E.A.F.); and Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Cleveland, OH (J.D.S., S.L.H.). J.E.F. is currently affiliated with Department of Medicine (Cardiology), Mount Sinai School of Medicine, New York, NY. B.H. is currently affiliated with Medizinische Klinik f\u00fcr Kardiologie..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Hewing","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (Cardiology) and Cell Biology, Marc and Ruti Bell Vascular Biology Program, New York University School of Medicine, New York, NY (J.E.F., B.H., E.A.F.); and Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Cleveland, OH (J.D.S., S.L.H.). J.E.F. is currently affiliated with Department of Medicine (Cardiology), Mount Sinai School of Medicine, New York, NY. B.H. is currently affiliated with Medizinische Klinik f\u00fcr Kardiologie..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Smith","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (Cardiology) and Cell Biology, Marc and Ruti Bell Vascular Biology Program, New York University School of Medicine, New York, NY (J.E.F., B.H., E.A.F.); and Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Cleveland, OH (J.D.S., S.L.H.). J.E.F. is currently affiliated with Department of Medicine (Cardiology), Mount Sinai School of Medicine, New York, NY. B.H. is currently affiliated with Medizinische Klinik f\u00fcr Kardiologie..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley L.","family":"Hazen","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (Cardiology) and Cell Biology, Marc and Ruti Bell Vascular Biology Program, New York University School of Medicine, New York, NY (J.E.F., B.H., E.A.F.); and Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Cleveland, OH (J.D.S., S.L.H.). J.E.F. is currently affiliated with Department of Medicine (Cardiology), Mount Sinai School of Medicine, New York, NY. 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