title: Myocardial collagen matrix remodeling and congestive heart failure.
abstract: In chronic heart failure, the inter-relationship of the renin-angiotensin-aldosterone system (RAAS) and cardiac growth is of primary clinical interest. In the pressure or volume overloaded heart, hypertrophic growth of the myocardium includes the enlargement of cardiac myocytes--an adaptation governed by ventricular loading. Nonmyocyte cell growth involving cardiac fibroblast may also occur but not primarily regulated by the hemodynamic load. Cardiac fibroblast activation is responsible for the accumulation of fibrillar type I and type III collagens within the interstitium and adventitia of intramyocardial coronary arteries. In addition to relaxation abnormalities due to impairment of sarcoplasmic Ca(2+)-ATPase activity, this remodeling of the cardiac interstitium represents a major determinant of pathological hypertrophy in that it accounts for abnormal myocardial stiffness, leading to ventricular diastolic and systolic dysfunction and ultimately the appearance of symptomatic heart failure. In vivo and in vitro studies suggest that the effector hormones, angiotensin II and aldosterone, of the RAAS are primarily involved in regulating the structural remodeling of the myocardial collagen matrix. In cultured adult cardiac fibroblasts, angiotensin II and aldosterone have been shown to stimulate collagen synthesis while angiotensin II additionally inhibits matrix metalloproteinase 1 activity, which is the key enzyme for interstitial collagen degradation in the myocardium. These observations may serve as rationale why angiotensin converting enzyme inhibition or blockade of the RAAS represents such remedial therapy in congestive heart failure in patients with hypertensive heart disease, post-myocardial infarction or with dilated cardiomyopathy.
authors.affiliation: Division of Cardiology, Philipps-University of Marburg, Germany.
authors.forename: C G
authors.initials: CG
authors.lastname: Brilla
authors.forename: H
authors.initials: H
authors.lastname: Rupp
mesh_terms: D006332:Cardiomegaly / Q000209:etiology / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D005355:Fibrosis; D006333:Heart Failure / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D009206:Myocardium / Q000473:pathology*; D012084:Renin-Angiotensin System
chemical_list: D003094:Collagen