1. Role of ageing and coronary atherosclerosis in the development of cardiac fibrosis in the rabbit
- Author
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Luigi Giusto Spagnoli, Amedeo Ferlosio, Augusto Orlandi, Arianna Francesconi, and Marcella Marcellini
- Subjects
Male ,Aging ,Ageing ,Atherosclerosis ,Endothelial function ,Extracellular matrix ,Remodeling ,Pathology ,medicine.medical_specialty ,Nitric Oxide Synthase Type III ,Endothelium ,Physiology ,Cardiac fibrosis ,Vascular Cell Adhesion Molecule-1 ,Cell Count ,Coronary Artery Disease ,Settore MED/08 - Anatomia Patologica ,Coronary artery disease ,Transforming Growth Factor beta ,Fibrosis ,Physiology (medical) ,In Situ Nick-End Labeling ,Animals ,Medicine ,Myocytes, Cardiac ,Endothelial dysfunction ,Coronary atherosclerosis ,business.industry ,medicine.disease ,Coronary Vessels ,Immunohistochemistry ,Actins ,medicine.anatomical_structure ,Coronary vessel ,Myocardial fibrosis ,Endothelium, Vascular ,Rabbits ,Nitric Oxide Synthase ,Cardiology and Cardiovascular Medicine ,business - Abstract
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 (TGFβ-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 TGFβ-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 TGFβ-1-positive myofibroblasts and interstitial inflammation were the major findings in atherosclerotic old rabbits, whereas with ageing alone, interstitial fibrosis with TGFβ-1 negative fibroblasts and VCAM-1 positive microvessels prevailed.
- Published
- 2004