1. Fibroblasts and the extracellular matrix in right ventricular disease.
- Author
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Frangogiannis NG
- Subjects
- Animals, Arrhythmogenic Right Ventricular Dysplasia pathology, Arrhythmogenic Right Ventricular Dysplasia physiopathology, Extracellular Matrix pathology, Extracellular Matrix Proteins metabolism, Fibroblasts pathology, Fibrosis, Heart Failure etiology, Heart Failure metabolism, Heart Failure pathology, Heart Failure physiopathology, Humans, Hypertension, Pulmonary complications, Hypertension, Pulmonary metabolism, Hypertension, Pulmonary pathology, Hypertension, Pulmonary physiopathology, Hypertrophy, Right Ventricular etiology, Hypertrophy, Right Ventricular pathology, Hypertrophy, Right Ventricular physiopathology, Myocardial Infarction pathology, Myocardial Infarction physiopathology, Myocardium pathology, Ventricular Dysfunction, Right etiology, Ventricular Dysfunction, Right pathology, Ventricular Dysfunction, Right physiopathology, Arrhythmogenic Right Ventricular Dysplasia metabolism, Extracellular Matrix metabolism, Fibroblasts metabolism, Hypertrophy, Right Ventricular metabolism, Myocardial Infarction metabolism, Myocardium metabolism, Ventricular Dysfunction, Right metabolism, Ventricular Function, Right, Ventricular Remodeling
- Abstract
Right ventricular failure predicts adverse outcome in patients with pulmonary hypertension (PH), and in subjects with left ventricular heart failure and is associated with interstitial fibrosis. This review manuscript discusses the cellular effectors and molecular mechanisms implicated in right ventricular fibrosis. The right ventricular interstitium contains vascular cells, fibroblasts, and immune cells, enmeshed in a collagen-based matrix. Right ventricular pressure overload in PH is associated with the expansion of the fibroblast population, myofibroblast activation, and secretion of extracellular matrix proteins. Mechanosensitive transduction of adrenergic signalling and stimulation of the renin-angiotensin-aldosterone cascade trigger the activation of right ventricular fibroblasts. Inflammatory cytokines and chemokines may contribute to expansion and activation of macrophages that may serve as a source of fibrogenic growth factors, such as transforming growth factor (TGF)-β. Endothelin-1, TGF-βs, and matricellular proteins co-operate to activate cardiac myofibroblasts, and promote synthesis of matrix proteins. In comparison with the left ventricle, the RV tolerates well volume overload and ischemia; whether the right ventricular interstitial cells and matrix are implicated in these favourable responses remains unknown. Expansion of fibroblasts and extracellular matrix protein deposition are prominent features of arrhythmogenic right ventricular cardiomyopathies and may be implicated in the pathogenesis of arrhythmic events. Prevailing conceptual paradigms on right ventricular remodelling are based on extrapolation of findings in models of left ventricular injury. Considering the unique embryologic, morphological, and physiologic properties of the RV and the clinical significance of right ventricular failure, there is a need further to dissect RV-specific mechanisms of fibrosis and interstitial remodelling., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2017
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