Immunologic Effects of the Renin-Angiotensin System.

Published

Journal Article (Review)

Inappropriate activation of the renin-angiotensin system (RAS) exacerbates renal and vascular injury. Accordingly, treatment with global RAS antagonists attenuates cardiovascular risk and slows the progression of proteinuric kidney disease. By reducing BP, RAS inhibitors limit secondary immune activation responding to hemodynamic injury in the target organ. However, RAS activation in hematopoietic cells has immunologic effects that diverge from those of RAS stimulation in the kidney and vasculature. In preclinical studies, activating type 1 angiotensin (AT1) receptors in T lymphocytes and myeloid cells blunts the polarization of these cells toward proinflammatory phenotypes, protecting the kidney from hypertensive injury and fibrosis. These endogenous functions of immune AT1 receptors temper the pathogenic actions of renal and vascular AT1 receptors during hypertension. By counteracting the effects of AT1 receptor stimulation in the target organ, exogenous administration of AT2 receptor agonists or angiotensin 1-7 analogs may similarly limit inflammatory injury to the heart and kidney. Moreover, although angiotensin II is the classic effector molecule of the RAS, several RAS enzymes affect immune homeostasis independently of canonic angiotensin II generation. Thus, as reviewed here, multiple components of the RAS signaling cascade influence inflammatory cell phenotype and function with unpredictable and context-specific effects on innate and adaptive immunity.

Full Text

Duke Authors

Cited Authors

  • Crowley, SD; Rudemiller, NP

Published Date

  • May 2017

Published In

Volume / Issue

  • 28 / 5

Start / End Page

  • 1350 - 1361

PubMed ID

  • 28151411

Pubmed Central ID

  • 28151411

Electronic International Standard Serial Number (EISSN)

  • 1533-3450

Digital Object Identifier (DOI)

  • 10.1681/ASN.2016101066

Language

  • eng

Conference Location

  • United States