The endothelial cyclooxygenase pathway: Insights from mouse arteries

To date, cyclooxygenase-2 (COX-2) is commonly believed to be the major mediator of endothelial prostacyclin (prostaglandin I-2; PGI(2)) synthesis that balances the effect of thromboxane (Tx) A2 synthesis mediated by the other COX isoform, COX-1 in platelets. Accordingly, selective inhibition of COX-2 is considered to cause vasoconstriction, platelet aggregation, and hence increase the incidence of cardiovascular events. This idea has been claimed to be substantiated by experiments on mouse models, some of which are deficient in one of the two COX isoforms. However, results from our studies and those of others using similar mouse models suggest that COX-1 is the major functional isoform in vascular endothelium. Also, although PGI(2) is recognized as a potent vasodilator, in some arteries endothelial COX activation causes vasoconstrictor response. This has again been recognized by studies, especially those performed on mouse arteries, to result largely from endothelial PGI(2) synthesis. Therefore, evidence that supports a role for COX-1 as the major mediator of PGI(2) synthesis in mouse vascular endothelium, reasons for the inconsistency, and results that elucidate underlying mechanisms for divergent vasomotor reactions to endothelial COX activation will be discussed in this review. In addition, we address the possible pathological implications and limitations of findings obtained from studies performed on mouse arteries. (C) 2016 Published by Elsevier B.V.