Angiotensin II and Vascular Injury

Authors: Augusto C Montezano Aurelie Nguyen Dinh Cat Francisco J Rios Rhian M Touyz

Publish Date: 2014/04/24

Volume: 16, Issue: 6, Pages: 431-

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Abstract

Vascular injury characterized by endothelial dysfunction structural remodelling inflammation and fibrosis plays an important role in cardiovascular diseases Cellular processes underlying this include altered vascular smooth muscle cell VSMC growth/apoptosis fibrosis increased contractility and vascular calcification Associated with these events is VSMC differentiation and phenotypic switching from a contractile to a proliferative/secretory phenotype Inflammation associated with macrophage infiltration and increased expression of redoxsensitive proinflammatory genes also contributes to vascular remodelling Among the many factors involved in vascular injury is Ang II Ang II previously thought to be the sole biologically active downstream peptide of the reninangiotensin system RAS is converted to smaller peptides Ang III Ang IV Ang17 that are functional and that modulate vascular tone and structure The actions of Ang II are mediated via signalling pathways activated upon binding to AT1R and AT2R AT1R activation induces effects through PLCIP3DAG MAP kinases tyrosine kinases tyrosine phosphatases and RhoA/Rho kinase Ang II elicits many of its pathophysiological actions by stimulating reactive oxygen species ROS generation through activation of vascular NADPH oxidase Nox ROS in turn influence redoxsensitive signalling molecules Here we discuss the role of Ang II in vascular injury focusing on molecular mechanisms and cellular processes Implications in vascular remodelling inflammation calcification and atherosclerosis are highlightedStudies performed by RMT were supported by grants from the Canadian Institutes of Health Research CIHR JDRF and the British Heart Foundation BHF RMT is supported through a BHF Chair ACM is supported by a Leadership fellowship from the University of Glasgow

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