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

Studies with sPLA(2) Group X, and cPLA(2)alpha gene-targeted mice suggest that absence of sPLA(2) Group X results in protection from ischemia/reperfusion (I/R) injury in the heart, and absence of cPLA(2)alpha Group IV is protective in the brain. Although latter studies might suggest a similar deleterious role for cPLA(2)alpha 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, cPLA(2)alpha((-/-)) 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 cPLA(2)alpha((-/-)) versus cPLA(2)alpha((+/+)) mice. This suggests that cPLA(2)alpha does not have an important cardiomyocyte autonomous effect on ischemic injury. Prostaglandin E-2 (PGE(2)) levels are significantly reduced in the hearts of the cPLA(2)alpha((-/-)) mice, and the enhanced injury is ameliorated by treatment with the PGE analog, misoprostol. We demonstrate that cPLA(2)alpha is cardioprotective in vivo, and this is likely via cPLA(2)alpha-mediated production of cardioprotective eicosanoids. These studies are the first to identify a protective role for cPLA(2) in I/R injury in any organ and raise concerns over long-term inhibition of cPLA(2). Clin Trans Sci 2011; Volume 4: 236-242