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

Abstract

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.

High density lipoproteins and endothelial functions: mechanistic insights and alterations in cardiovascular disease

“…The impact of HDL on prostacyclin production in endothelium occurs by both the provision of arachidonate ( 178,180,183 ) and upregulation of Cox-2 expression ( 184,185 ). It has also been observed that HDL3 induces Cox-2 expression and prostacyclin release via a p38 MAPK/CREB-dependent pathway in the endothelium (185)(186)(187)(188). Recently, it was demonstrated that apoA-I, but not apoA-II, induced the expression of Cox-2 and the production of prostacyclin through the p38 MAPK, ERK1/2, and JAK2 pathways via ABCA1 in endothelial cells ( 189 ).…”

Hypoxia upregulates PGI-synthase and increases PGI2 release in human vascular cells exposed to inflammatory stimuli

“…COX-2 has commonly been associated with pro-infl ammatory/proatherogenic stages, due to its upregulation at infl ammatory sites such as active atherosclerotic lesions. However, COX-2 is constitutively expressed in the endothelium ( 13,14 ), is upregulated by atheroprotective lipoproteins in vascular cells (15)(16)(17), and seems to contribute to the innate defensive mechanism of the myocardium ( 18,19 ). Indeed, the pathophysiological meaning of COX-2 induction in a particular setting depends on the activity of downstream enzymes that transform PGH 2 into different prostanoids in a cell-type-specifi c manner ( 12,20 ).…”

High‐Density Lipoprotein: A Novel Target for Antirestenosis Therapy

“…12 Moreover, HDL impedes vascular SMCs proliferation and S-phase entry, and this results from the upregulation of prostacyclin (PGI2) and cyclooxygenase-2 (COX-2) expression. 149,150 HDL has also been found to inhibit PDGFinduced migration of vascular SMCs, which is attributed to the S1P2 receptor-dependent manner. 151,152 Studies of vascular SMCs and rat aortic explants have revealed the HDL-dependent inhibition of MCP-1 production was accompanied by the suppression of ROS, which is associated with SR-BI and S1P3 receptor in vascular SMCs, suggesting inhibition of NAD(P) H oxidase activity by HDL-associated lysosphingolipids may constitute an important mechanism by which HDL exerts its potent antiatherogenic effects.…”

“…Second, HDL inhibits inflammatory chemokine‐stimulated proliferation of SMCs, which may be related to the SR‐BI‐dependent deactivation of PI3K/AKT pathway . Moreover, HDL impedes vascular SMCs proliferation and S‐phase entry, and this results from the up‐regulation of prostacyclin (PGI2) and cyclooxygenase‐2 (COX‐2) expression . HDL has also been found to inhibit PDGF‐induced migration of vascular SMCs, which is attributed to the S1P2 receptor‐dependent manner .…”