Angiotensin II revisited: new roles in inflammation, immunology and aging

Ariela Benigni,Giuseppe Remuzzi,Paola Cassis

doi:10.1002/emmm.201000080

Ariela Benigni, Giuseppe Remuzzi + Show 1 more

Open Access

https://doi.org/10.1002/emmm.201000080

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Abstract

That the renin–angiotensin system (RAS) is involved in regulation of blood pressure, vasoconstriction, sodium intake and potassium excretion is well established. Studies in the last few years have however documented new roles for this molecule as a pro-inflammatory molecule and more recently as a possible pro-fibrotic agent that contributes to progressive deterioration of organ function in disease. Binding of Ang II to its receptors (in particular AT1) mediates intracellular free radical generation that contributes to tissue damage by promoting mitochondrial dysfunction. Blocking Ang II signalling protects against neurodegenerative processes and promotes longevity in rodents. Altogether these findings open the unanticipated perspective for exploring Ang II signalling in therapeutic interventions in inflammatory diseases and aging-related tissue injury. This review extends from the discovery of Ang II and its implications in renal and cardiovascular physiology to cover the roles of the system in inflammation, tissue injury, autoimmunity, oxidative stress and aging.

Highlights

II to its receptors mediates intracellular free radical generation that contributes to tissue damage by promoting mitochondrial dysfunction
This review extends from the discovery of angiotensin II (Ang II) and its implications in renal and cardiovascular physiology to cover the roles of the system responses (Yun et al, 2006)
Zhou et al have recently followed up on this suggestion and showed that pregnant mice injected with purified AT1-autoantibodies from women with preeclampsia develop typical signs of this condition such as hypertension, proteinuria, glomerular endotheliosis and placental abnormalities, all features that could be prevented by losartan administration (Zhou et al, 2008)

Summary

In Focus

Received March 08, 2010 / Revised June 03, 2010 / Accepted June 07, 2010. That the renin–angiotensin system (RAS) is involved in regulation of blood pressure, vasoconstriction, sodium intake and potassium excretion is well established. Studies in the last few years have documented new roles for this molecule as a proinflammatory molecule and more recently as a possible pro-fibrotic agent that contributes to progressive deterioration of organ function in disease.

Introduction

Angiotensin II and Autoimmunity

Does Brain Ras Affect Cognitive Functions During Aging?

Clinical Implications

Findings

How does Ang II modulate TLR expression and activity in inflammation?