Neurohumoral modulation of metalloproteinases in cardiac failure: impact on remodeling
A dominant hallmark of cardiac failure is progressive chamber dilation and structural remodeling. This process is thought to play a major contributory role to the later stages of chamber dysfunction and is linked to increased morbidity and mortality in various clinical studies [9, 16, 28]. The magnitude of dilation far exceeds anything achievable with acute loading stress, but rather involves structural rearrangement within the myocardial wall notably of the fibrillar collagen matrix surrounding myocytes and blood vessels. This process of collagen degradation and remodeling is principally mediated by matrix metalloproteinases (MMPs), a large family of enzymes synthesized by several myocardial cell types, and secreted and activated within the cardiac interstitium [3, 5, 38, 39, 41]. Recent studies have reported elevation of MMP expression in failing experimental and human heart failure [21, 36, 38]. Furthermore, inhibition of this enzyme system has been shown to limit progressive chamber dilation both in a rodent infarct model , and in cardiac failure induced by rapid ventricular pacing in the pig , supporting a role in chamber remodeling.
KeywordsCardiac Failure Rapid Pace Chamber Dilation Diastolic Stiffening Cardiac Interstitium
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