Role of TGF-beta 1 in platelet-mediated cardioprotection during ischemia-reperfusion in isolated rat hearts

Platelets protect myocardium against ischemia-reperfusion injury, This stud y examined the role of platelet-derived TGF-beta(1) in cardioprotection dur ing ischemia-reperfusion. Isolated Sprague Dawley rat hearts were perfused with K-H buffer and subjected to 25 min of global ischemia followed by 30 m in 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 attenua ted (P < 0.01) of myocardial dysfunction following ischemia-reperfusion. Is chemia-reperfusion resulted in a decrease in myocardial TGF-beta(1) determi ned by immunohistochemistry. ELISA showed an increase in latent TGF-beta(1) , but a decrease in active TGF-beta(1), Perfusion of hearts with platelets or aggregated platelet supernatant preserved myocardial TGF-beta(1) content upon ischemia-reperfusion, Perfusion of hearts with recombinant TGF-beta(1 ) also resulted in cardioprotection following ischemia-reperfusion qualitat ively similar to that observed with platelets or aggregated platelet supern atants. RT-PCR analysis showed an increase in myocardial TGF-beta(1) mRNA f ollowing ischemia-reperfusion. These observations indicate that platelets p rotect the myocardium against ischemia-reperfusion-mediated dysfunction at least in part by releasing TGF-beta(1), Increase in both TGF-beta(1) mRNA a nd latent TGF-beta(1) does not indicate a defect in the translation of mRNA , Reduction in myocardial TGF-beta(1) following ischemia-reperfusion sugges ts a defect in the conversion of latent TGF-beta(1) to active TGF-beta(1).