Abstract
Atherosclerosis is a multi-factorial inflammatory disease with accumulation of lipids and recruitment of leukocytes into the subendothelial space. Due to the consistent inflammation in vessels, a subset of atherosclerotic plaques is even prone to physical disruption or producing thrombosis that triggers acute coronary syndromes (ACS).
Cyclooxygenase (COX) and the downstream diverse prostanoids are involved in numerous physiological activities and inflammatory processes. Remarkably, prostanoids are a group of bioactive lipid mediators, and play a series of complicated and even contradictory roles during the progression of atherogenesis. Some, mainly prostacyclin (PGI2) have cardioprotective effects to inhibit the aggravation of atherosclerosis, however, others including prostaglandin E2 (PGE2) and thromboxane A2 (TXA2), increase the risk of cardiovascular thromboembolic events. Therefore, the controversial effects bring about a debate on the use of cyclooxygenase-2 (COX-2) specific and non-specific inhibitors in the prevention from cardiovascular diseases. In addition to reverse cholesterol transport (RCT), high-density lipoprotein (HDL) exerts several beneficial effects on endothelial protection. Moreover, HDL could also regulate the expression of COX-2 and the production of PGI2 in endothelial cells. While as a diverse complex of heterogeneous particle composed of various apolipoproteins, enzymes and lipids, the individual components of HDL, such as apolipoprotein A-I (apoA-I) and sphingosine-1-phosphate (S1P), have distinct effects on COX-2 expression and PGI2 production in endothelial cells. In the present review, we summarize the roles of COX-2 as well as PGI2 in atherosclerosis and atherothrombosis, the controversial vascular effects on prostanoid inhibition by COX-2 inhibitors, and the effects of HDL on the endothelial protection by the upregulation of COX-2 and the release of PGI2 during the progression of atherosclerosis.Keywords: Cyclooxygenase-2 (COX-2), prostacyclin (PGI2), high-density lipoprotein (HDL), endothelial cell
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