Role of TGF-beta1 in platelet-mediated cardioprotection during ischemia-reperfusion in isolated rat hearts.
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
J L
JL
Department of Medicine, University of Florida College of Medicine and VA Medical Center, Gainesville 32610, USA. mehta@medmac.ufl.edu
Yang
B C
BC
Strates
B S
BS
Mehta
P
P
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006321:Heart / Q000033:anatomy & histology / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000097:blood / Q000502:physiology*
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta