Background: High-density lipoproteins (HDLs) induce prostacyclin (PGI2) 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 PGI2 synthesis in human VSMCs and to assess the impact that the intake of diets with different fatty acid composition exert on HDL-induced PGI2 release.
Materials and methods: Human VSMCs were treated with HDL or fatty acids in the presence or absence of different cell signalling inhibitors and PGI2 (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 PGI2 synthesis and Cox-2 up-regulation, while arachidonic acid (AA) but not other fatty acids mimicked the effects of HDL. Arachidonic acid induced PGI2 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 PGI2 release than that from the PUFA n-6 period (64% vs. 100%).
Conclusions: Our results suggest that lipid moiety modulates HDL-induced PGI2 release/Cox-2 up-regulation in human VSMCs, and that changes in fatty acids as accomplished with the diet can modulate vascular PGI2 homeostasis.