01 - FUNCTIONAL INTERACTION BETWEEN APOLIPOPROTEINS A2 AND E IN THE REGULATION OF PLASMA CHOLESTEROL AND TRIGLYCERIDES LEVELS
Serafoula Filou, Christina P Kalogeropoulou · 2019
Functional interaction between apolipoproteins A2 and E in the regulation of plasma cholesterol and triglycerides levelsSerafoula Filou, Evangelia Zvintzou, Christina Kalogeropoulou, Eva Xepapadaki and Kyriakos E. KypreosUniversity of Patras, School of Medicine, Department of Pharmacology, Rio Achaias, TK. 26500, GreeceAim: Apolipoprotein A2 (APOA2) plays crucial role in HDL synthesis, function and plasma concentration. Accumulation of exchangeable apolipoproteins on HDL prevents their association with triglyceride rich lipoproteins (TRL) and the subsequent inhibition of lipoprotein lipase, resulting in physiological plasma triglyceride levels. Here, we investigated the role of APOA2-rich HDL in the regulation of plasma TRL metabolism.Methods: We created a recombinant attenuated adenovirus expressing human APOA2 and the green Fluorescent protein (GFP) under the independent control of two CMV promoters (AdGFP-A2). Then, Apoa1-deficient (apoa1-/-) mice fed western-type diet for 2 weeks were infected with AdGFP-A2, or a control adenovirus expressing only GFP (AdGFP). Since APOE is a known modulator of plasma triglyceride metabolism, these mice were compared to mice with concomitant deficiency in Apoa1 and Apoe (apoa1-/- x apoe-/-) infected with the same viruses. Biochemical analyses were then performed. Results: APOA2 expression in apoa1-/- mice resulted in an increase of plasma triglyceride levels. In contrast, in apoa1-/- x apoe-/- mice, APOA2 reduced their initially elevated cholesterol and triglyceride levels found in VLDL and LDL, suggesting a positive effect on their dyslipidemia. Kinetic analysis following intravenous injection of Triton WR1339 showed significant reduction in the rate of VLDL triglyceride production only in AdGFP-A2 infected apoa1-/- x apoe-/- mice. Conclusions: The effects of APOA2-HDL on plasma lipoprotein metabolism are significantly modified by endogenous functional Apoe. Given the role of VLDL and LDL in atherosclerosis, the importance of this functional interaction in the pathogenesis of the disease is currently under further investigation.