Experimental and interventional dietary study in humans on the role of HDL fatty acid composition in PGI2 release and Cox-2 expression by VSMC

Background High-density lipoproteins (HDLs) induce prostacyclin (PGI(2)) release in vascular smooth muscle cells ( VSMCs) by up-regulation of cyclooxygenase-2 ( Cox-2). Our goal was to analyze the role of human HDL lipid moiety on Cox-2-dependent PGI(2) synthesis in human VSMCs and to assess the impact that the intake of diets with different fatty acid composition exert on HDL-induced PGI(2) release. Materials and methods Human VSMCs were treated with HDL or fatty acids in the presence or absence of different cell signalling inhibitors and PGI(2) ( by enzyme immunoassay) and Cox-2 protein levels ( by Western blot) were analyzed. High-density lipoproteins were obtained from a plasma pool or from plasma of 12 volunteers subjected to a longitudinal dietary interventional study of three consecutive diets periods enriched in monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids n-6 ( PUFA n-6) or n- 3 ( PUFA n- 3). Results High-density lipoprotein delipidation attenuated the effect of HDL on both PGI(2) synthesis and Cox-2 up-regulation, while arachidonic acid ( AA) but not other fatty acids mimicked the effects of HDL. Arachidonic acid induced PGI(2) synthesis and Cox-2 expression through similar mechanisms to those activated by HDL [ pertussis toxin-sensitive G proteins, p42/44 mitogen-activated protein kinase (MAPK), p38MAPK, and c-Jun N-terminal kinase-1 ( JNK-1) pathways]. Finally, we observed that HDL from the PUFA n-3 dietary period induced lower PGI(2) release than that from the PUFA n-6 period (64% vs. 100%). Conclusions Our results suggest that lipid moiety modulates HDL- induced PGI(2) release/ Cox-2 up-regulation in human VSMCs, and that changes in fatty acids as accomplished with the diet can modulate vascular PGI(2) homeostasis.