Increased cholesterol efflux capacity in metabolic syndrome: Relation with qualitative alterations in HDL and LCAT. Issue 1 (September 2015)

• Record Type: Journal Article
• Authors: Lucero, Diego; Svidirov, Denis; Freeman, Lita; López, Graciela I.; Fassio, Eduardo; Remaley, Alan T.; Schreier, Laura
• Is Part Of: Atherosclerosis. Volume 242:Issue 1(2015)
• Page Start: 236
• Page End: 242
• Publication Date: 2015-09
• Subjects: Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2015.07.019
• Languages: English
• ISSNs: 0021-9150

Abstract

<abstract xml:lang="en" abstract-type="author" id="abs0010"> <title id="sectitle0010">Abstract</title> <sec> <title id="sectitle0015">Background</title> <p id="abspara0010">Metabolic syndrome (MetS) is associated with changes in HDL levels, composition and sub-fraction profile. Whether these alterations affect HDL anti-atherogenic function, specifically measured as its capacity to perform cholesterol efflux, is not yet clearly known.</p> </sec> <sec> <title id="sectitle0020">Objective</title> <p id="abspara0015">To evaluate the relation between serum cholesterol efflux capacity and the changes in HDL composition and sub-fraction profile in MetS.</p> </sec> <sec> <title id="sectitle0025">Methods</title> <p id="abspara0020">In 35 non-treated MetS patients and 15 healthy controls, HDL mediated cholesterol efflux was measured as the ability of apoB-depleted serum to accept cholesterol from cholesterol-loaded BHK cells expressing either ABCA1 or ABCG1. Additionally we determined: lipid profile, HDL sub-fractions (NMR) and LCAT mass (ELISA). Isolated HDL (δ:1.063–1.210 g/mL) was chemically characterized. Pre-β1-HDL was determined by 2D-electrophoresis in a sub-group of MetS and controls (n = 6 each).</p> </sec> <sec> <title id="sectitle0030">Results</title> <p id="abspara0025">Surprisingly, MetS patients presented higher ABCA1 mediated cholesterol efflux (10.4 ± 1.8 <italic>vs.</italic> 8.7 ± 0.3%; p = 0.0001), without differences in ABCG1 efflux. In MetS, HDL showed reduction in particle size and number (p < 0.02) and lower large/small HDL ratio (p = 0.05), as well as triglyceride enrichment (p = 0.0001). Pre-β1-HDL was increased in MetS (p = 0.048) and correlated with ABCA1-cholesterol efflux (r = 0.64; p = 0.042). LCAT mass showed a tendency to reduction in MetS (p = 0.08), and inversely correlated with ABCA1-cholesterol efflux (r = −0.51; p = 0.001), independently of obesity and insulin-resistance (β = −0.40, p = 0.034).</p> </sec> <sec> <title id="sectitle0035">Conclusion</title> <p id="abspara0030">This is the first description of ABCA1 mediated cholesterol efflux in MetS. Regardless the reduced HDL-cholesterol, <italic>in vitro</italic> cholesterol efflux capacity by ABCA1 was enhanced, linked to increased pre-β1-HDL and slightly reduced in LCAT mass that would probably reflect a delay in reverse cholesterol transport occurring in MetS.</p> </sec> </abstract>