title: The interaction between Hsp70 and TNF-alpha expression: a novel mechanism for protection of the myocardium against post-injury depression.
abstract: Tumor necrosis factor-alpha (TNF-alpha) depresses myocardial contractility, and overexpression of TNF-alpha in the myocardium contributes to cardiac dysfunction caused by both systemic and local insults. Sepsis, endotoxemia, hemorrhagic shock, and myocardial ischemia-reperfusion all promote cardiac dysfunction in part by a TNF-alpha-mediated mechanism. Thus, TNF-alpha represents an appealing therapeutic target for myocardial protection against multiple clinically relevant insults. The inducible 70-kD heat shock protein (Hsp70) is expressed in the myocardium in response to stress and has been linked to enhanced myocardial resistance to depression associated with ischemia-reperfusion or sepsis. The mechanism by which Hsp70 protects cardiac function against a subsequent insult remains obscure. In vitro induction of Hsp70 in monocytes or macrophages inhibits TNF-alpha production following bacterial lipopolysaccharide stimulation, and in vivo induction of Hsp70 down-regulates tissue TNF-alpha production following an injurious insult. Understanding of the regulatory role of Hsp70 in the myocardial inflammatory response will provide insights into the mechanism by which Hsp70 preserves cardiac function and may yield therapies for protection of the myocardium against depression associated injurious insults.
authors.affiliation: Department of Surgery, University of Colorado Health Sciences Center, Denver, USA.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Meng
authors.forename: Alden H
authors.initials: AH
authors.lastname: Harken
mesh_terms: D000818:Animals; D019446:Endotoxemia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D006331:Heart Diseases / Q000209:etiology* / Q000628:therapy; D006801:Humans; D017202:Myocardial Ischemia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D016328:NF-kappa B / Q000378:metabolism; D018805:Sepsis / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D012771:Shock, Hemorrhagic / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D018840:HSP70 Heat-Shock Proteins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha