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Myofibroblast-mediated mechanisms of pathological remodelling of the heart.
MedLine Citation:
PMID:  23207731     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The syncytium of cardiomyocytes in the heart is tethered within a matrix composed principally of type I fibrillar collagen. The matrix has diverse mechanical functions that ensure the optimal contractile efficiency of this muscular pump. In the diseased heart, cardiomyocytes are lost to necrotic cell death, and phenotypically transformed fibroblast-like cells-termed 'myofibroblasts'-are activated to initiate a 'reparative' fibrosis. The structural integrity of the myocardium is preserved by this scar tissue, although at the expense of its remodelled architecture, which has increased tissue stiffness and propensity to arrhythmias. A persisting population of activated myofibroblasts turns this fibrous tissue into a living 'secretome' that generates angiotensin II and its type 1 receptor, and fibrogenic growth factors (such as transforming growth factor-β), all of which collectively act as a signal-transducer-effector signalling pathway to type I collagen synthesis and, therefore, fibrosis. Persistent myofibroblasts, and the resultant fibrous tissue they produce, cause progressive adverse myocardial remodelling, a pathological hallmark of the failing heart irrespective of its etiologic origin. Herein, we review relevant cellular, subcellular, and molecular mechanisms integral to cardiac fibrosis and consequent remodelling of atria and ventricles with a heterogeneity in cardiomyocyte size. Signalling pathways that antagonize collagen fibrillogenesis provide novel strategies for cardioprotection.
Authors:
Karl T Weber; Yao Sun; Syamal K Bhattacharya; Robert A Ahokas; Ivan C Gerling
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-04
Journal Detail:
Title:  Nature reviews. Cardiology     Volume:  -     ISSN:  1759-5010     ISO Abbreviation:  Nat Rev Cardiol     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101500075     Medline TA:  Nat Rev Cardiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Division of Cardiovascular Diseases, University of Tennessee Health Science Center, 956 Court Avenue, Suite A312, Memphis, TN 38163, USA.
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