Angiotensin II and Vascular Injury

Overview

Journal Curr Hypertens Rep

Specialty Cardiology & Vascular Diseases

Date 2014 Apr 25

PMID 24760441

Citations 164

Authors

Augusto C Montezano

Aurelie Nguyen Dinh Cat

Francisco J Rios

Rhian M Touyz

Affiliations

Soon will be listed here.

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 redox-sensitive pro-inflammatory 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 renin-angiotensin system (RAS), is converted to smaller peptides, [Ang III, Ang IV, Ang-(1-7)], 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 PLC-IP3-DAG, MAP kinases, tyrosine kinases, tyrosine phosphatases and RhoA/Rho kinase. Ang II elicits many of its (patho)physiological actions by stimulating reactive oxygen species (ROS) generation through activation of vascular NAD(P)H oxidase (Nox). ROS in turn influence redox-sensitive 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 highlighted.

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References

Wilkinson-Berka J, Agrotis A, Deliyanti D . The retinal renin-angiotensin system: roles of angiotensin II and aldosterone. Peptides. 2012; 36(1):142-50. DOI: 10.1016/j.peptides.2012.04.008. View

Shaltout H, Figueroa J, Rose J, Diz D, Chappell M . Alterations in circulatory and renal angiotensin-converting enzyme and angiotensin-converting enzyme 2 in fetal programmed hypertension. Hypertension. 2008; 53(2):404-8. PMC: 2674380. DOI: 10.1161/HYPERTENSIONAHA.108.124339. View

Tsai K, Chen L, Chiou S, Chiou G, Chen Y, Chou H . Coenzyme Q10 suppresses oxLDL-induced endothelial oxidative injuries by the modulation of LOX-1-mediated ROS generation via the AMPK/PKC/NADPH oxidase signaling pathway. Mol Nutr Food Res. 2011; 55 Suppl 2:S227-40. DOI: 10.1002/mnfr.201100147. View

Bregeon J, Loirand G, Pacaud P, Rolli-Derkinderen M . Angiotensin II induces RhoA activation through SHP2-dependent dephosphorylation of the RhoGAP p190A in vascular smooth muscle cells. Am J Physiol Cell Physiol. 2009; 297(5):C1062-70. DOI: 10.1152/ajpcell.00174.2009. View

Montezano A, Touyz R . Molecular mechanisms of hypertension--reactive oxygen species and antioxidants: a basic science update for the clinician. Can J Cardiol. 2012; 28(3):288-95. DOI: 10.1016/j.cjca.2012.01.017. View

Sampaio W, de Castro C, Santos R, Schiffrin E, Touyz R . Angiotensin-(1-7) counterregulates angiotensin II signaling in human endothelial cells. Hypertension. 2007; 50(6):1093-8. DOI: 10.1161/HYPERTENSIONAHA.106.084848. View

Montezano A, Burger D, Paravicini T, Chignalia A, Yusuf H, Almasri M . Nicotinamide adenine dinucleotide phosphate reduced oxidase 5 (Nox5) regulation by angiotensin II and endothelin-1 is mediated via calcium/calmodulin-dependent, rac-1-independent pathways in human endothelial cells. Circ Res. 2010; 106(8):1363-73. PMC: 3119893. DOI: 10.1161/CIRCRESAHA.109.216036. View

Ferreira P, Dos Santos R, Campagnole-Santos M . Angiotensin-(3-7) pressor effect at the rostral ventrolateral medulla. Regul Pept. 2007; 141(1-3):168-74. DOI: 10.1016/j.regpep.2006.12.031. View

Delva P, Lechi A, Pastori C, Degan M, Sheiban I, Montesi G . Collagen I and III mRNA gene expression and cell growth potential of skin fibroblasts in patients with essential hypertension. J Hypertens. 2002; 20(7):1393-9. DOI: 10.1097/00004872-200207000-00026. View

10.

Kasal D, Barhoumi T, Li M, Yamamoto N, Zdanovich E, Rehman A . T regulatory lymphocytes prevent aldosterone-induced vascular injury. Hypertension. 2011; 59(2):324-30. DOI: 10.1161/HYPERTENSIONAHA.111.181123. View

11.

Henrion D, Kubis N, Levy B . Physiological and pathophysiological functions of the AT(2) subtype receptor of angiotensin II: from large arteries to the microcirculation. Hypertension. 2001; 38(5):1150-7. DOI: 10.1161/hy1101.096109. View

12.

Kobayashi N, Nakano S, Mita S, Kobayashi T, Honda T, Tsubokou Y . Involvement of Rho-kinase pathway for angiotensin II-induced plasminogen activator inhibitor-1 gene expression and cardiovascular remodeling in hypertensive rats. J Pharmacol Exp Ther. 2002; 301(2):459-66. DOI: 10.1124/jpet.301.2.459. View

13.

He Y, Yao G, Savoia C, Touyz R . Transient receptor potential melastatin 7 ion channels regulate magnesium homeostasis in vascular smooth muscle cells: role of angiotensin II. Circ Res. 2004; 96(2):207-15. DOI: 10.1161/01.RES.0000152967.88472.3e. View

14.

Akishita M, Horiuchi M, Yamada H, Zhang L, Shirakami G, Tamura K . Inflammation influences vascular remodeling through AT2 receptor expression and signaling. Physiol Genomics. 2000; 2(1):13-20. DOI: 10.1152/physiolgenomics.2000.2.1.13. View

15.

Santos R, Frezard F, Ferreira A . Angiotensin-(1-7): blood, heart, and blood vessels. Curr Med Chem Cardiovasc Hematol Agents. 2005; 3(4):383-91. DOI: 10.2174/156801605774322373. View

16.

Ocaranza M, Jalil J . Protective Role of the ACE2/Ang-(1-9) Axis in Cardiovascular Remodeling. Int J Hypertens. 2012; 2012:594361. PMC: 3270559. DOI: 10.1155/2012/594361. View

17.

Li X, Yang H, Giachelli C . BMP-2 promotes phosphate uptake, phenotypic modulation, and calcification of human vascular smooth muscle cells. Atherosclerosis. 2008; 199(2):271-7. PMC: 3249145. DOI: 10.1016/j.atherosclerosis.2007.11.031. View

18.

Suematsu M, Suzuki H, DeLano F, Schmid-Schonbein G . The inflammatory aspect of the microcirculation in hypertension: oxidative stress, leukocytes/endothelial interaction, apoptosis. Microcirculation. 2002; 9(4):259-76. DOI: 10.1038/sj.mn.7800141. View

19.

Bader M . ACE2, angiotensin-(1–7), and Mas: the other side of the coin. Pflugers Arch. 2013; 465(1):79-85. DOI: 10.1007/s00424-012-1120-0. View

20.

Bruder-Nascimento T, Chinnasamy P, Riascos-Bernal D, Cau S, Callera G, Touyz R . Angiotensin II induces Fat1 expression/activation and vascular smooth muscle cell migration via Nox1-dependent reactive oxygen species generation. J Mol Cell Cardiol. 2014; 66:18-26. PMC: 3943818. DOI: 10.1016/j.yjmcc.2013.10.013. View