Angiotensin II and Cardiovascular Disease: Balancing Pathogenic and Protective Pathways

Figures

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  Figure 1. Renin-Angiotensin Aldosterone System and its receptors. Through the enzymatic activity of renin, angiotensinogen is converted to angiotensin I, which is then further metabolised to angiotensin II by ACE or to angiotensin (1-9) by ACE II. Angiotensin II, the active peptide of the renin-angiotensin system, exhibits opposing effects on the cardiovascular system through activation of AT1R or AT2R. Angiotensin II can also be converted to angiotensin (1-7) by ACE II. Both angiotensin (1-9) and angiotensin (1-7) reduce blood pressure (BP). Angiotensin (1-9) exerts its effects by binding to MasR. Angiotensin III, formed by the metabolism of angiotensin II via aminopeptidase A, regulates BP through its effects on ANP and vasopressin. Angiotensin IV, generated from angiotensin III by aminopeptidase N, plays important roles in the modulation of cognitive functions and cerebral blood flow. ACE, angiotensin-converting enzyme; ANP, atrial natriuretic peptide; AT1R, angiotensin II type 1 receptor; AT2R, angiotensin II type 2 receptor; BP, blood pressure; MasR, Mas receptor; VSMC, vascular smooth muscle cell.

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  Figure 2. Angiotensin II exerts its functions by binding to AT1R and AT2R. Activation of AT1R leads to increases in BP, oxidative stress, cytokine and chemokine release, EC senescence, and ageing through induction of various signalling pathways and TFs, e.g., protein kinase C, Janus kinases, and c-myc. Activation of AT2R exerts opposite effects to those mediated by AT1R. AT1R, angiotensin II type 1 receptor; AT2R, angiotensin II type 2 receptor; BP, blood pressure; cGMP, cyclic guanosine monophosphate; EC, endothelial cell; TFs, transcription factors; VSMC, vascular smooth muscle cell; MEK, mitogen-activated protein kinase; NO, nitric oxide.

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  Figure 3. Angiotensin II exerts both cardiovascular protective and destructive effects. By binding to its type 2 receptor (AT2R), ang II triggers the release of nitric oxide and, consequently, promotes vascular relaxation while suppressing cell proliferation and apoptosis. By binding to its type receptor (AT1R), ang II increases BP and evokes vasoconstriction, oxidative stress, and inflammation. Elevations in oxidative stress and inflammation stimulate vascular cell proliferation, migration, and differentiation, leading to endothelial dysfunction and atherosclerosis. Through atherosclerotic disease formation and its direct effects on vascular tone and blood pressure, ang II contributes to the development of myocardial infarction, cardiovascular remodelling, and stroke. BP, blood pressure; NO, nitric oxide; ED, endothelial dysfunction; PKC, protein kinase C; PDGF, platelet-derived growth factor; bFGF, basic fibroblast growth factor.