| First Author | Saito Y | Year | 2012 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 302 |
| Issue | 10 | Pages | H2018-30 |
| PubMed ID | 22427514 | Mgi Jnum | J:186740 |
| Mgi Id | MGI:5432992 | Doi | 10.1152/ajpheart.00955.2011 |
| Citation | Saito Y, et al. (2012) Disruption of group IVA cytosolic phospholipase A(2) attenuates myocardial ischemia-reperfusion injury partly through inhibition of TNF-alpha-mediated pathway. Am J Physiol Heart Circ Physiol 302(10):H2018-30 |
| abstractText | Group IVA cytosolic phospholipase A(2) (cPLA(2)alpha), which preferentially cleaves arachidonic acid from phospholipids, plays a role in apoptosis and tissue injury. Downstream signals in response to tumor necrosis factor (TNF)-alpha, a mediator of myocardial ischemia-reperfusion (I/R) injury, involve cPLA(2)alpha activation. This study examined the potential role of cPLA(2)alpha and its mechanistic link with TNF-alpha in myocardial I/R injury using cPLA(2)alpha knockout (cPLA(2)alpha(-/-)) mice. Myocardial I/R was created with 10-wk-old male mice by 1 h ligation of the left anterior descending coronary artery, followed by 24 h of reperfusion. As a result, compared with wild-type (cPLA(2)alpha(+/+)) mice, cPLA(2)alpha(-/-) mice had a 47% decrease in myocardial infarct size, preservation of echocardiographic left ventricle (LV) function (%fractional shortening: 14 vs. 21%, respectively), and lower content of leukotriene B(4) and thromboxane B(2) (62 and 50% lower, respectively) in the ischemic myocardium after I/R. Treatment with the TNF-alpha inhibitor (soluble TNF receptor II/IgG1 Fc fusion protein, sTNFR:Fc) decreased myocardial I/R injury and LV dysfunction in cPLA(2)alpha(+/+) mice but not cPLA(2)alpha(-/-) mice. sTNFR:Fc also suppressed cPLA(2)alpha phosphorylation in the ischemic myocardium after I/R of cPLA(2)alpha(+/+) mice. Similarly, sTNFR:Fc exerted protective effects against hypoxia-reoxygenation (H/R)-induced injury in the cultured cardiomyocytes from cPLA(2)alpha(+/+) mice but not cPLA(2)alpha(-/-) cardiomyocytes. H/R and TNF-alpha induced cPLA(2)alpha phosphorylation in cPLA(2)alpha(+/+) cardiomyocytes, which was reversible by sTNFR:Fc. In cPLA(2)alpha(-/-) cardiomyocytes, TNF-alpha induced apoptosis and release of arachidonic acid to a lesser extent than in cPLA(2)alpha(+/+) cardiomyocytes. In conclusion, disruption of cPLA(2)alpha attenuates myocardial I/R injury partly through inhibition of TNF-alpha-mediated pathways. |
