Inflammatory mediators and reversible myocardial dysfunction.
A variety of seemingly unrelated clinical conditions manifest the same effects on the heart. These effects include: (1) reversible myocardial dysfunction, (2) beta-adrenergic desensitization, and (3) activation of inflammatory mediators. We provide evidence supporting a role for cytokines, mitogen activated protein kinases (MAP kinases), and nitric oxide (NO) as common mediators of reversible myocardial dysfunction and beta-adrenergic desensitization. Data from animal models and human studies support a pathogenic role for these inflammatory mediators in ischemic as well as non-ischemic myocardial dysfunction. It is suggested that compensatory cellular programs are activated to provide short-term protection from brief periods of ischemia and infection. Continuous activation of these compensatory pathways leads to cardiomyopathy and chronic (congestive) heart failure. Elucidating the signaling pathways involved has the potential to provide the opportunity to exploit the cardioprotective advantages of these agents without bearing the burden of excessive stimulation.
Kan
Hong
H
Department of Medicine (Cardiology), Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine, Morgantown, West Virginia, USA.
Finkel
Mitchell S
MS
D000818:Animals; D009202:Cardiomyopathies / Q000276:immunology / Q000503:physiopathology*; D006333:Heart Failure / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D009200:Myocardial Contraction; D009206:Myocardium / Q000276:immunology / Q000378:metabolism*; D020127:Recovery of Function; D015398:Signal Transduction
D018836:Inflammation Mediators