Activation and release of degradative proteinases within the myocardium are the trigger for ventricular remodeling in chronic heart failure.
Our conceptual framework of chronic heart failure is based upon the neurohormonal model. In this construct, neurohormonal systems that provide short-term homeostasis remain activated after a myocardial injury, producing progressive ventricular dysfunction and worsening heart failure. However, this model fails to explain several aspects of the pathophysiology of heart failure, including the mechanisms that trigger neurohoromone release and those that lead to ventricular dysfunction in the absence of a large myocardial infarction. These gaps in our understanding can be explained by an expanded model of heart failure, which focuses on myocardial matrix events as the triggers for disease progression. This model embraces the neurohormonal model, and integrates the roles of the immune system and the myocardial fibroblast, within the matrix, to more fully describe the initiation and progression of the disease.
Sackner-Bernstein
J D
JD
Division of Cardiology, St Luke's-Roosevelt Hospital Center, New York, NY 10025, USA. jsackner-bernstein@slrhc.org
D002908:Chronic Disease; D010450:Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000473:pathology; D006333:Heart Failure / Q000473:pathology*; D006352:Heart Ventricles / Q000473:pathology*; D006801:Humans; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology
D010450:Endopeptidases