Vascular fibrosis in aging and hypertension: molecular mechanisms and clinical implications

Harvey, A., Montezano, A. C., Lopes, R. A. , Rios, F. and Touyz, R. (2016) Vascular fibrosis in aging and hypertension: molecular mechanisms and clinical implications. Canadian Journal of Cardiology, 32(5), pp. 659-668. (doi: 10.1016/j.cjca.2016.02.070) (PMID:27118293) (PMCID:PMC4906153)

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Abstract

Aging is the primary risk factor underlying hypertension and incident cardiovascular disease. With aging, the vasculature undergoes structural and functional changes characterized by endothelial dysfunction, wall thickening, reduced distensibility, and arterial stiffening. Vascular stiffness results from fibrosis and extracellular matrix (ECM) remodelling, processes that are associated with aging and are amplified by hypertension. Some recently characterized molecular mechanisms underlying these processes include increased expression and activation of matrix metalloproteinases, activation of transforming growth factor-β1/SMAD signalling, upregulation of galectin-3, and activation of proinflammatory and profibrotic signalling pathways. These events can be induced by vasoactive agents, such as angiotensin II, endothelin-1, and aldosterone, which are increased in the vasculature during aging and hypertension. Complex interplay between the “aging process” and prohypertensive factors results in accelerated vascular remodelling and fibrosis and increased arterial stiffness, which is typically observed in hypertension. Because the vascular phenotype in a young hypertensive individual resembles that of an elderly otherwise healthy individual, the notion of “early” or “premature” vascular aging is now often used to describe hypertension-associated vascular disease. We review the vascular phenotype in aging and hypertension, focusing on arterial stiffness and vascular remodelling. We also highlight the clinical implications of these processes and discuss some novel molecular mechanisms of fibrosis and ECM reorganization.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Rios, Dr Francisco and Harvey, Dr Adam and Alves Moreira Lopes, Dr Rheure and Montezano, Dr Augusto and Touyz, Professor Rhian
Authors: Harvey, A., Montezano, A. C., Lopes, R. A., Rios, F., and Touyz, R.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Canadian Journal of Cardiology
Publisher:Pulsus Group Inc
ISSN:0828-282X
ISSN (Online):1916-7075
Published Online:03 March 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Canadian Journal of Cardiology 32(5):659-668
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
607382Vascular Noxs as therapeutic targets and biomarkers in hypertensionRhian TouyzBritish Heart Foundation (BHF)RG/13/7/30099RI CARDIOVASCULAR & MEDICAL SCIENCES
607381Vascular Noxs as therapeutic targets and biomarkers in hypertensionRhian TouyzBritish Heart Foundation (BHF)CH/12/4/29762RI CARDIOVASCULAR & MEDICAL SCIENCES