title: The endothelial cyclooxygenase pathway: Insights from mouse arteries.
abstract: To date, cyclooxygenase-2 (COX-2) is commonly believed to be the major mediator of endothelial prostacyclin (prostaglandin I2; PGI2) 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 PGI2 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 PGI2 synthesis. Therefore, evidence that supports a role for COX-1 as the major mediator of PGI2 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.
authors.affiliation: Central Lab, Shantou University Medical College, Shantou, China.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Luo
authors.affiliation: Cardiovascular Research Center, Shantou University Medical College, Shantou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Cardiovascular Research Center, Shantou University Medical College, Shantou, China. Electronic address: zhouyingbi35@gmail.com.
authors.forename: Yingbi
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001158:Arteries / Q000166:cytology*; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D051379:Mice
chemical_list: D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
keywords: Arachidonic acid metabolism; Contraction; Prostacyclin; Prostacyclin receptors; Relaxation; Thromboxane-prostanoid receptors