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Role of renin-angiotensin system in inflammation, immunity and aging

Luciano S A Capettini1, Fabrizio Montecucco, Francois Mach

  • 1Laboratory of Hemodynamics and Cardiovascular Technology, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Switzerland. luciano.capettini@epfl.ch

Current Pharmaceutical Design
|January 31, 2012
PubMed

Insights

The Renin-Angiotensin System (RAS) influences more than just cardiovascular health, impacting cell growth, senescence, and inflammation. Emerging research highlights the ACE2/Ang-(1-7)/Mas receptor axis as a key regulator in these processes.

Area of Science:

  • Immunology
  • Endocrinology
  • Cell Biology

Background:

  • The Renin-Angiotensin System (RAS) traditionally impacts cardiovascular and renal functions.
  • Recent findings reveal RAS involvement in modulating cellular processes like free radical production, cytokine synthesis, cell growth, senescence, and migration.
  • The classic ACE/Ang II/AT1R pathway is linked to inflammation, senescence, and autoimmune issues via ROS production and pro-inflammatory cytokine release.

Purpose of the Study:

  • To review the novel roles of classical and new RAS components.
  • To explore the implications of RAS in physiological aging, the immune system, and inflammation.
  • To update the understanding of the ACE2/Ang-(1-7)/Mas receptor axis as a counter-regulatory pathway.

Main Methods:

  • Literature review of recent data on RAS components and their functions.
  • Analysis of studies investigating the ACE/Ang II/AT1R and ACE2/Ang-(1-7)/Mas receptor pathways.
  • Examination of the role of RAS in aging, immunity, and inflammation.

Main Results:

  • The classic RAS activation (ACE/Ang II/AT1R) downregulates pro-survival genes, increases ROS, and promotes inflammation and senescence.
  • The ACE2/Ang-(1-7)/Mas receptor axis emerges as a counter-regulator, potentially controlling cytokine release, cell migration, and preventing apoptosis.
  • RAS blockers show potential as anti-inflammatory and immunomodulatory agents, with possible applications in autoimmune diseases.

Conclusions:

  • The RAS plays a multifaceted role beyond cardiovascular regulation, significantly influencing cellular functions, aging, and immune responses.
  • The ACE2/Ang-(1-7)/Mas receptor pathway represents a critical counterbalance to the detrimental effects of the classic RAS.
  • Further research into RAS modulation, particularly the ACE2 axis, may offer new therapeutic strategies for inflammatory and autoimmune conditions.

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