Immunologic Effects of the Renin-Angiotensin System.
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 AT1receptors temper the pathogenic actions of renal and vascular AT1receptors during hypertension. By counteracting the effects of AT1receptor stimulation in the target organ, exogenous administration of AT2receptor 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.
Division of Nephrology, Department of Medicine, Durham Veterans Affairs and Duke University Medical Centers, Durham, North Carolina steven.d.crowley@duke.edu.
Steven D
SD
Crowley
Division of Nephrology, Department of Medicine, Durham Veterans Affairs and Duke University Medical Centers, Durham, North Carolina.
Nathan P
NP
Rudemiller
D000803:Angiotensin I / Q000502:physiology; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D006801:Humans; D010446:Peptide Fragments / Q000502:physiology; D007703:Peptidyl-Dipeptidase A / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology; D012084:Renin-Angiotensin System / Q000276:immunology*
D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)
hypertension; immunology; renin angiotensin system