Diego Lucero1, Denis Sviridov, Denis Svidirov2, Lita Freeman2, Graciela I López3, Eduardo Fassio4, Alan T Remaley2, Laura Schreier3. 1. Laboratory of Lipids and Atherosclerosis, Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, INFIBIOC, University of Buenos Aires, Argentina; Lipoprotein Metabolism Section, National Heart, Lung, Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. Electronic address: dmlucero@ffyb.uba.ar. 2. Lipoprotein Metabolism Section, National Heart, Lung, Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. 3. Laboratory of Lipids and Atherosclerosis, Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, INFIBIOC, University of Buenos Aires, Argentina. 4. Department of Gastroenterology, National Hospital "Prof. A. Posadas", Buenos Aires, Argentina.
Abstract
BACKGROUND: 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. OBJECTIVE: To evaluate the relation between serum cholesterol efflux capacity and the changes in HDL composition and sub-fraction profile in MetS. METHODS: 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). RESULTS: Surprisingly, MetS patients presented higher ABCA1 mediated cholesterol efflux (10.4 ± 1.8 vs. 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). CONCLUSION: This is the first description of ABCA1 mediated cholesterol efflux in MetS. Regardless the reduced HDL-cholesterol, in vitro 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.
BACKGROUND: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. OBJECTIVE: To evaluate the relation between serum cholesterol efflux capacity and the changes in HDL composition and sub-fraction profile in MetS. METHODS: 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). RESULTS: Surprisingly, MetS patients presented higher ABCA1 mediated cholesterol efflux (10.4 ± 1.8 vs. 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). CONCLUSION: This is the first description of ABCA1 mediated cholesterol efflux in MetS. Regardless the reduced HDL-cholesterol, in vitro 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.
Authors: Arthur McCullough; Stephen F Previs; Jaividhya Dasarathy; Kwangwon Lee; Abdullah Osme; Chunki Kim; Serguei Ilchenko; Shuhui W Lorkowski; Jonathan D Smith; Srinivasan Dasarathy; Takhar Kasumov Journal: Am J Physiol Endocrinol Metab Date: 2019-09-10 Impact factor: 4.310
Authors: Wijtske Annema; Arne Dikkers; Jan Freark de Boer; Marleen M J van Greevenbroek; Carla J H van der Kallen; Casper G Schalkwijk; Coen D A Stehouwer; Robin P F Dullaart; Uwe J F Tietge Journal: Sci Rep Date: 2016-06-08 Impact factor: 4.379
Authors: Julie Gall; Eric Frisdal; Randa Bittar; Wilfried Le Goff; Eric Bruckert; Philippe Lesnik; Maryse Guerin; Philippe Giral Journal: J Am Heart Assoc Date: 2016-11-23 Impact factor: 5.501
Authors: Timo Paavola; Sanna Kuusisto; Matti Jauhiainen; Sakari Kakko; Tiia Kangas-Kontio; Jari Metso; Pasi Soininen; Mika Ala-Korpela; Risto Bloigu; Minna L Hannuksela; Markku J Savolainen; Tuire Salonurmi Journal: PLoS One Date: 2017-02-16 Impact factor: 3.240
Authors: Charlotte P J Talbot; Ronald P Mensink; Lotte Smolders; Virginie Bakeroot; Jogchum Plat Journal: Mol Nutr Food Res Date: 2018-06-19 Impact factor: 5.914
Authors: Mark S Borja; Bradley Hammerson; Chongren Tang; Olga V Savinova; Gregory C Shearer; Michael N Oda Journal: PLoS One Date: 2017-08-02 Impact factor: 3.240