Mediation of cardioprotection by transforming growth factor-beta.
Myocardial ischemia causes heart injury that is characterized by an increase in circulating tumor necrosis factor (TNF), the local production of superoxide anions, the loss of coronary vasodilation (relaxation) in response to agents that release endothelial cell relaxation factor, and cardiac tissue damage. Ischemic injury can be mimicked by TNF. When given before or immediately after ischemic injury, transforming growth factor-beta (TGF-beta) reduced the amount of superoxide anions in the coronary circulation, maintained endothelial-dependent coronary relaxation, and reduced injury mediated by exogenous TNF. Thus, TGF-beta prevented severe cardiac injury, perhaps by alleviating damage mediated by increases in circulating TNF.
Lefer
A M
AM
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Tsao
P
P
Aoki
N
N
Palladino
M A
MA
D000818:Animals; D003327:Coronary Disease / Q000517:prevention & control*; D003402:Creatine Kinase / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D008297:Male; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*; D009924:Organ Culture Techniques; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism; D015291:Transforming Growth Factors / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D015291:Transforming Growth Factors; D003402:Creatine Kinase