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Revista chilena de cardiología

On-line version ISSN 0718-8560

Abstract

MENDOZA, Camila et al. Effect of ciprofibrate on HDL cholesterol metabolism and plasma anti-oxidant capacity in mice. Rev Chil Cardiol [online]. 2016, vol.35, n.2, pp.133-143. ISSN 0718-8560.  http://dx.doi.org/10.4067/S0718-85602016000200006.

Background: Increased serum levels of LDL cholesterol and/or decreased values of HDL cholesterol are very relevant for atherosclerotic cardiovascular disease. Low HDL cholesterol is the most prevalent dyslipidemia in the Chilean population. Regarding reduced HDL cholesterol and high triglyceride levels, fibrates, nuclear receptor PPAR-a agonists that modulate transcription of genes involved in lipid metabolism, represent an important alternative for pharmacological management of dyslipidemia. However, recent clinical studies have been inconclusive with respect to their real benefit on atherosclerosis when used in combination with statins. Aim: To evaluate the impact of fibrate administration on HDL cholesterol metabolism and antioxidant plasma functionality using the mouse as experimental model. Methodology: Using wild-type C57BL/6 mice, ciprofibrate was administered at 0.2% in chow diet for 7 days. After treatment, plasma cholesterol and triglycerides levels, hepatic expression of key proteins involved in HDL cholesterol metabolism, liver cholesterol content, biliary cholesterol secretion, and plasma oxidative damage and antioxidant function were analyzed. Results: Ciprofibrate treatment significantly decreased plasma triglycerides levels and hepatic HDL receptor SR-BI expression. This latter finding was associated with increased HDL particle size, without changes in HDL cholesterol levels. Furthermore, ci-profibrate decreased hepatic expression of cholesterol transporters ABCG1 and ABCG8, but not ABCA1, which correlated with reduced liver cholesterol content and increased biliary cholesterol secretion. Fina-lly, fibrate therapy improved plasma antioxidant func-tion, even though increased nitrosative plasma protein damage was detected. Conclusion: This study has provided new information on metabolic and functional effects derived from fibrate use in mice and it may help to better understand recent clinical findings using this lipid-lowering drug class in humans.

Keywords : HDL cholesterol; HDL functionality; Atherosclerosis; PPAR-a; ciprofibrate.

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