Platelets protect the myocardium against ischemia-reperfusion-mediated dysfunction at least in part by releasing TGF-beta1.
Platelets protect myocardium against ischemia-reperfusion injury. This study examined the role of platelet-derived TGF-beta1 in cardioprotection during ischemia-reperfusion. Isolated Sprague Dawley rat hearts were perfused with K-H buffer and subjected to 25 min of global ischemia followed by 30 min of reperfusion. Ischemia-reperfusion resulted in myocardial dysfunction indicated by increase in CPP and LVEDP, and decrease in dLVP. Perfusion of hearts with washed platelets or supernatant of aggregated platelets attenuated (P < 0.01) of myocardial dysfunction following ischemia-reperfusion. Ischemia-reperfusion resulted in a decrease in myocardial TGF-beta1 determined by immunohistochemistry. ELISA showed an increase in latent TGF-beta1, but a decrease in active TGF-beta1. Perfusion of hearts with platelets or aggregated platelet supernatant preserved myocardial TGF-beta1 content upon ischemia-reperfusion. Perfusion of hearts with recombinant TGF-beta1 also resulted in cardioprotection following ischemia-reperfusion qualitatively similar to that observed with platelets or aggregated platelet supernatants. RT-PCR analysis showed an increase in myocardial TGF-beta1 mRNA following ischemia-reperfusion. These observations indicate that platelets protect the myocardium against ischemia-reperfusion-mediated dysfunction at least in part by releasing TGF-beta1. Increase in both TGF-beta1 mRNA and latent TGF-beta1 does not indicate a defect in the translation of mRNA. Reduction in myocardial TGF-beta1 following ischemia-reperfusion suggests a defect in the conversion of latent TGF-beta1 to active TGF-beta1.
Mehta et al. (Fri,) studied this question.