Interplay between Oxidative Stress, Cyclooxygenases, and Prostanoids in Cardiovascular Diseases

Significance: Endothelial cells lining the lumen of blood vessels play an important role in the regulation of cardiovascular functions through releasing both vasoconstricting and vasodilating factors. The production and function of vasoconstricting factors are largely elevated in hypertension, diabetes, atherosclerosis, and ischemia/reperfusion injuries. Cyclooxygenases (COXs) are the major enzymes producing five different prostanoids that act as either contracting or relaxing substances. Under conditions of increased oxidative stress, the expressions and activities of COX isoforms are altered, resulting in changes in production of various prostanoids and thus affecting vascular tone. This review briefly summarizes the relationship between oxidative stress, COXs, and prostanoids, thereby providing new insights into the pathophysiological mechanisms of cardiovascular diseases (CVDs). 
Recent Advances: Many new drugs targeting oxidative stress, COX-2, and prostanoids against common CVDs have been evaluated in recent years and they are summarized in this review. 
Critical Issues: Comprehensive understanding of the complex interplay between oxidative stress, COXs, and prostanoids in CVDs helps develop more effective measures against cardiovascular pathogenesis. 
Future Directions: Apart from minimizing the undesired effects of harmful prostanoids, future studies shall investigate the restoration of vasoprotective prostanoids as a means to combat CVDs. Antioxid. Redox Signal. 34, 784-799.