Document Detail


Role of ageing and coronary atherosclerosis in the development of cardiac fibrosis in the rabbit.
MedLine Citation:
PMID:  15537508     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Myocardial fibrosis contributes to the impairing of cardiac function and characterizes ageing, but is also a consequence of atherosclerotic ischemic disease. Since atherosclerosis is a slow progressive disease, which prevails in elderly populations, the aim of this study was to distinguish the contribution of ageing and atherosclerosis to cardiac fibrosis. METHODS: Coronary atherosclerosis was induced in 5-6-year-old rabbits by a hyperlipemic diet for 9 months. Left ventricular (LV) collagen was quantified by densitometric analysis after Sirius-Red staining; an immunohistochemical investigation of the interstitium was also performed. RESULTS: Atherosclerosis was associated to a marked increase of left ventricular interstitial collagen with the appearance of fibrotic foci and a decrease of coronary vessel endothelial nitric oxide synthase (eNOS) expression. In fibrotic foci, abundant macrophages co-localized with transforming growth factor beta-1 (TGFbeta-1)-positive myofibroblasts and vascular cell adhesion molecule-1 (VCAM-1) positive microvessels (52.3+/-3.9%). In normocholesterolemic rabbits, ageing resulted in a fourfold increase of myocardial interstitial collagen, with alpha-smooth muscle actin and TGFbeta-1 negative fibroblasts and VCAM-1 positive microvessels (19.4+/-1.2%) without macrophages, suggesting a role of endothelial dysfunction in age-related fibrosis. CONCLUSIONS: There is a distinct difference between ageing and coronary atherosclerosis-induced cardiac fibrosis, although the effects may be cumulative. In the cascade of events leading to myocardial remodeling, reparative fibrosis with TGFbeta-1-positive myofibroblasts and interstitial inflammation were the major findings in atherosclerotic old rabbits, whereas with ageing alone, interstitial fibrosis with TGFbeta-1 negative fibroblasts and VCAM-1 positive microvessels prevailed.
Authors:
Augusto Orlandi; Arianna Francesconi; Marcella Marcellini; Amedeo Ferlosio; Luigi Giusto Spagnoli
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cardiovascular research     Volume:  64     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2004 Dec 
Date Detail:
Created Date:  2004-11-11     Completed Date:  2005-02-17     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  544-52     Citation Subset:  IM    
Affiliation:
Department of Biopathology and Image Diagnostics, Anatomic Pathology Institute, Tor Vergata University of Rome, Via della Ricerca Scientifica, 00133 Rome, Italy. orlandi@uniroma2.it
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MeSH Terms
Descriptor/Qualifier:
Actins / analysis,  metabolism
Aging / physiology*
Animals
Cell Count
Coronary Artery Disease / metabolism,  pathology*
Coronary Vessels / pathology
Endothelium, Vascular / chemistry,  metabolism,  pathology*
Extracellular Matrix / metabolism,  pathology
Fibrosis
Immunohistochemistry / methods
In Situ Nick-End Labeling
Male
Myocytes, Cardiac / metabolism,  pathology*
Nitric Oxide Synthase / analysis,  metabolism
Nitric Oxide Synthase Type III
Rabbits
Transforming Growth Factor beta / analysis,  metabolism
Vascular Cell Adhesion Molecule-1 / analysis,  metabolism
Chemical
Reg. No./Substance:
0/Actins; 0/Transforming Growth Factor beta; 0/Vascular Cell Adhesion Molecule-1; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type III

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