Cytosolic Phospholipase A2α Protects against Ischemia/Reperfusion Injury in the Heart

Studies with sPLA2 Group X, and cPLA2α gene‐targeted mice suggest that absence of sPLA2 Group X results in protection from ischemia/reperfusion (I/R) injury in the heart, and absence of cPLA2α Group IV is protective in the brain. Although latter studies might suggest a similar deleterious role for cPLA2α in I/R injury in the heart, the pathophysiology of stroke is intricately related to excitotoxicity and cannot necessarily be extrapolated to the heart. We report here that unlike findings in the brain, cPLA2α(−/−) mice have exaggerated injury following I/R in vivo. In contrast, there is no difference in injury induced by simulated ischemia in cardiomyocytes isolated from cPLA2α(−/−) versus cPLA2α(+/+) mice. This suggests that cPLA2α does not have an important cardiomyocyte autonomous effect on ischemic injury. Prostaglandin E2 (PGE2) levels are significantly reduced in the hearts of the cPLA2α(−/−) mice, and the enhanced injury is ameliorated by treatment with the PGE analog, misoprostol. We demonstrate that cPLA2α is cardioprotective in vivo, and this is likely via cPLA2α‐mediated production of cardioprotective eicosanoids. These studies are the first to identify a protective role for cPLA2 in I/R injury in any organ and raise concerns over long‐term inhibition of cPLA2. Clin Trans Sci 2011; Volume 4: 236–242