Structural remodelling of the heart by fibrous tissue: role of circulating hormones and locally produced peptides.
Symptomatic heart failure is accompanied by diastolic ventricular dysfunction due largely to an extensive reactive and reparative fibrosis. Experimental evidence suggests a clear association between myocardial fibrosis and chronic inappropriate elevations in circulating angiotensin II (Ang II) and/or aldosterone. Although not entirely elucidated, injury follows Ang II-associated release of adrenal medullary catecholamines and aldosterone-induced myocardial potassium depletion. Increasing evidence indicates locally produced cardiac Ang II plays an important role in tissue repair that may underlie myocardial remodelling, the fibrous tissue accumulation both at and remote to the site of myocardial infarction (MI). Angiotensin converting enzyme (ACE) binding density markedly increases at these fibrous tissue sites after experimental MI, indicating an involvement in wound healing regardless of the cause and location of fibrosis; cells expressing Ang II receptors are primarily myofibroblasts. Therapy with ACE inhibitors and aldosterone receptor antagonist have each been shown to attenuate development of fibrosis.
Weber
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KT
Department of Internal Medicine, University of Missouri Health Sciences Center, Columbia 65212, USA.
Sun
Y
Y
Campbell
S E
SE
D000450:Aldosterone / Q000502:physiology*; D000804:Angiotensin II / Q000502:physiology*; D002306:Cardiac Volume / Q000502:physiology; D002395:Catecholamines / Q000502:physiology; D003971:Diastole / Q000502:physiology; D004699:Endocardium / Q000473:pathology; D004719:Endomyocardial Fibrosis / Q000473:pathology*; D006333:Heart Failure / Q000473:pathology*; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D009206:Myocardium / Q000473:pathology*; D010455:Peptides / Q000502:physiology*; D007703:Peptidyl-Dipeptidase A / Q000502:physiology; D014945:Wound Healing / Q000502:physiology
D002395:Catecholamines; D010455:Peptides; D000804:Angiotensin II; D000450:Aldosterone; D007703:Peptidyl-Dipeptidase A