Vascular inflammation and the renin-angiotensin system

Allan R. Brasier, Adrian Recinos, Mohsen S. Eledrisi, Marschall S. Runge

Research output: Contribution to journalArticle

475 Citations (Scopus)

Abstract

It is now well established that vascular inflammation is an independent risk factor for the development of atherosclerosis. In otherwise healthy patients, chronic elevations of circulating interleukin-6 or its biomarkers are predictors for increased risk in the development and progression of ischemic heart disease. Although multifactorial in etiology, vascular inflammation produces atherosclerosis by the continuous recruitment of circulating monocytes into the vessel wall and by contributing to an oxidant-rich inflammatory milieu that induces phenotypic changes in resident (noninflammatory) cells. In addition, the renin-angiotensin system (RAS) has important modulatory activities in the atherogenic process. Recent work has shown that angiotensin II (Ang II) has significant proinflammatory actions in the vascular wall, inducing the production of reactive oxygen species, inflammatory cytokines, and adhesion molecules. These latter effects on gene expression are mediated, at least in part, through the cytoplasmic nuclear factor-κB transcription factor. Through these actions, Ang II augments vascular inflammation, induces endothelial dysfunction, and, in so doing, enhances the atherogenic process. Our recent studies have defined a molecular mechanism for a biological positive-feedback loop that explains how vascular inflammation can be self-sustaining through upregulation of the vessel wall Ang II tone. Ang II produced locally by the inflamed vessel induces the synthesis and secretion of interleukin-6, a cytokine that induces synthesis of angiotensinogen in the liver through a janus kinase (JAK)/signal transducer and activator of transcription (STAT)-3 pathway. Enhanced angiotensinogen production, in turn, supplies more substrate to the activated vascular RAS, where locally produced Ang II synergizes with oxidized lipid to perpetuate atherosclerotic vascular inflammation. These observations suggest that one mechanism by which RAS antagonists prevent atherosclerosis is by reducing vascular inflammation. Moreover, antagonizing the vascular nuclear factor-κB and/or hepatic JAK/STAT pathways may modulate the atherosclerotic process.

Original languageEnglish (US)
Pages (from-to)1257-1266
Number of pages10
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume22
Issue number8
DOIs
StatePublished - 2002

Fingerprint

Renin-Angiotensin System
Blood Vessels
Inflammation
Angiotensin II
Janus Kinases
Angiotensinogen
Atherosclerosis
Interleukin-6
Cytokines
STAT3 Transcription Factor
Liver
Transducers
Oxidants
Myocardial Ischemia
Monocytes
Reactive Oxygen Species
Transcription Factors
Up-Regulation
Biomarkers
Lipids

Keywords

  • Angiotensin II
  • Angiotensinogen
  • Atherosclerosis
  • Hepatic acute-phase response
  • Interleukin-6

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Vascular inflammation and the renin-angiotensin system. / Brasier, Allan R.; Recinos, Adrian; Eledrisi, Mohsen S.; Runge, Marschall S.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 22, No. 8, 2002, p. 1257-1266.

Research output: Contribution to journalArticle

Brasier, Allan R. ; Recinos, Adrian ; Eledrisi, Mohsen S. ; Runge, Marschall S. / Vascular inflammation and the renin-angiotensin system. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2002 ; Vol. 22, No. 8. pp. 1257-1266.
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