Contrasting effects of arachidonic acid and docosahexaenoic acid membrane incorporation into cardiomyocytes on free cholesterol turnover

• Published in: Biochimica et biophysica acta 2014-10, Vol.1841 (10), p.1413-1421
• Main Authors: Doublet, Aline, Robert, Véronique, Vedie, Benoît, Rousseau-Ralliard, Delphine, Reboulleau, Anne, Grynberg, Alain, Paul, Jean-Louis, Fournier, Natalie
• Format: Article
• Language: English
• Subjects: Arachidonic ω6 polyunsaturated fatty acid; ATP binding cassette transporter A1; Cardiomyocytes; Cholesterol efflux; Cholesterol homeostasis; Development Biology; Docosahexaenoic ω3 polyunsaturated fatty acid; Life Sciences; Reproductive Biology
• ISSN: 1388-1981; 0006-3002; 1879-2618
• DOI: 10.1016/j.bbalip.2014.07.003

The preservation of a constant pool of free cholesterol (FC) is critical to ensure several functions of cardiomyocytes. We investigated the impact of the membrane incorporation of arachidonic acid (C20:4 ω6, AA) or docosahexaenoic acid (C22:6 ω3, DHA) as ω6 or ω3 polyunsaturated fatty acids (PUFAs) on cholesterol homeostasis in primary cultures of neonatal rat cardiac myocytes. We measured significant alterations to the phospholipid FA profiles, which had markedly different ω6/ω3 ratios between the AA and DHA cells (13 vs. 1). The AA cells showed a 2.7-fold lower cholesterol biosynthesis than the DHA cells. Overall, the AA cells showed 2-fold lower FC masses and 2-fold higher cholesteryl ester masses than the DHA cells. The AA cells had a lower FC to phospholipid ratio and higher triglyceride levels than the DHA cells. Moreover, the AA cells showed a 40% decrease in ATP binding cassette transporter A1 (ABCA1)-mediated and a 19% decrease in ABCG1-mediated cholesterol efflux than the DHA cells. The differences in cholesterol efflux pathways induced by AA or DHA incorporation were not caused by variations in ABCs transporter expression and were reduced when ABC transporters were overexpressed by exposure to LXR/RXR agonists. These results show that AA incorporation into cardiomyocyte membranes decreased the FC turnover by markedly decreasing the endogenous cholesterol synthesis and by decreasing the ABCA1- and ABCG1-cholesterol efflux pathways, whereas DHA had the opposite effects. We propose that these observations may partially contribute to the beneficial effects on the heart of a diet containing a high ω3/ω6 PUFA ratio. [Display omitted] •Constant membrane cholesterol level is critical for several cardiomyocyte functions.•We supplied rat cardiomyocytes with arachidonic (AA) or docosahexaenoic (DHA) acids.•AA membrane incorporation decreased the free cholesterol (FC) turnover.•AA reduced the endogenous FC synthesis and the ABCA1-mediated cholesterol efflux.•DHA had opposite effects on cholesterol homeostasis in cardiomyocytes.