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Angiotensin receptors as determinants of life span

  • Integrative Physiology
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Abstract

Angiotensin II (Ang II), the central product of renin-angiotensin system, has a role in the etiology of hypertension and in pathophysiology of cardiac and renal diseases in humans. Other functions of Ang II include effects on immune response, inflammation, cell growth and proliferation, which are largely mediated by Ang II type 1 receptor (AT1). Several experimental studies have demonstrated that Ang II acts through AT1 as a mediator of normal aging processes by increasing oxidant damage to mitochondria and in consequences by affecting mitochondrial function. Recently, our group has demonstrated that the inhibition of Ang II activity by targeted disruption of the Agtr1a gene encoding Ang II type 1A receptor (AT1A) in mice translates into marked prolongation of life span. The absence of AT1A protected multiple organs from oxidative damage and the alleviation of aging-like phenotype was associated with increased number of mitochondria and upregulation of the prosurvival gene sirtuin 3. AT1 receptor antagonists have been proven safe and well-tolerated for chronic use and are used as a key component of the modern therapy for hypertension and cardiac failure, therefore Ang II/AT1 pathway represents a feasible therapeutic strategy to prolong life span in humans.

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Abbreviations

RAS:

renin-angiotensin system

Ang II:

angiotensin II

ACE:

angiotensin converting enzyme

AT1 :

Ang II type 1 receptor

AT2 :

Ang II type 2 receptor

NO:

nitric oxide

eNOS:

endothelial nitric oxide synthase

ROS:

reactive oxygen species

ACEi:

angiotensin-converting enzyme inhibitors

ARBs:

angiotensin II receptor blockers

SIRT:

sirtuin

Nampt:

nicotinamide phosphoribosyltransferase

IGF-1:

insulin growth factor-1

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Acknowledgements

Paola Cassis is a recipient of a fellowship from Associazione Ricerca Trapianti (ART), Milan, Italy, and Sara Conti is a recipient of a fellowship from Fondazione Aiuti per la Ricerca sulle Malattie Rare (ARMR) in memory of Lidia D’Arcangelo, Bergamo, Italy. The research was partially supported by the European Commission within the EuReGene project (LSHG-CT-2004–005085).

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Authors and Affiliations

  1. Mario Negri Institute for Pharmacological Research, Via Gavazzeni, 11, 24125, Bergamo, Italy

    Paola Cassis, Sara Conti, Giuseppe Remuzzi & Ariela Benigni

  2. Unit of Nephrology and Dialysis, Azienda Ospedaliera, Ospedali Riuniti di Bergamo, Bergamo, Italy

    Giuseppe Remuzzi

Authors
  1. Paola Cassis
  2. Sara Conti
  3. Giuseppe Remuzzi
  4. Ariela Benigni

Corresponding author

Correspondence to Ariela Benigni.

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Cassis, P., Conti, S., Remuzzi, G. et al. Angiotensin receptors as determinants of life span. Pflugers Arch - Eur J Physiol 459, 325–332 (2010). https://doi.org/10.1007/s00424-009-0725-4

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