NOX and inflammation in the vascular adventitia

Gabor Csanyi, W. Robert Taylor, Patrick J. Pagano

Research output: Contribution to journalReview article

85 Citations (Scopus)

Abstract

Vascular inflammation has traditionally been thought to be initiated at the luminal surface and progress through the media toward the adventitial layer. In recent years, however, evidence has emerged suggesting that the vascular adventitia is activated early in a variety of cardiovascular diseases and that it plays an important role in the initiation and progression of vascular inflammation. Adventitial fibroblasts have been shown to produce substantial amounts of NAD(P)H oxidase-derived reactive oxygen species (ROS) in response to vascular injury. Additionally, inflammatory cytokines, lipids, and various hormones, implicated in fibroblast proliferation and migration, lead to recruitment of inflammatory cells to the adventitial layer and impairment of endothelium-dependent relaxation. Early in the development of vascular disease, there is clear evidence for progression toward a denser vasa vasorum which delivers oxygen and nutrients to an increasingly hypoxic and nutrient-deficient media. This expanded vascularization appears to provide enhanced delivery of inflammatory cells to the adventitia and outer media. Combined adventitial fibroblast and inflammatory cell-derived ROS therefore are expected to synergize their local effect on adventitial parenchymal cells, leading to further cytokine release and a feed-forward propagation of adventitial ROS production. In fact, data from our laboratory and others suggest a broader paracrine positive feedback role for adventitia-derived ROS in medial smooth muscle cell hypertrophy and neointimal hyperplasia. A likely candidate responsible for the adventitia-derived paracrine signaling across the vessel wall is the superoxide anion metabolite hydrogen peroxide, which is highly stable, cell permeant, and capable of activating downstream signaling mechanisms in smooth muscle cells, leading to phenotypic modulation of smooth muscle cells. This review addresses the role of adventitial NAD(P)H oxidase-derived ROS from a nontraditional, perivascular vantage of promoting vascular inflammation and will discuss how ROS derived from adventitial NAD(P)H oxidases may be a catalyst for vascular remodeling and dysfunction.

Original languageEnglish (US)
Pages (from-to)1254-1266
Number of pages13
JournalFree Radical Biology and Medicine
Volume47
Issue number9
DOIs
StatePublished - Nov 1 2009

Fingerprint

Adventitia
Blood Vessels
Reactive Oxygen Species
Inflammation
NADPH Oxidase
Fibroblasts
Muscle
Cells
Nutrients
Cytokines
Smooth Muscle Myocytes
Metabolites
Superoxides
Hydrogen Peroxide
Vasa Vasorum
Modulation
Paracrine Communication
Hormones
Oxygen
Feedback

Keywords

  • Adventitia
  • Fibroblast
  • Hypertrophy
  • NADPH oxidase
  • Paracrine
  • Reactive oxygen species
  • Vascular inflammation

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

NOX and inflammation in the vascular adventitia. / Csanyi, Gabor; Taylor, W. Robert; Pagano, Patrick J.

In: Free Radical Biology and Medicine, Vol. 47, No. 9, 01.11.2009, p. 1254-1266.

Research output: Contribution to journalReview article

Csanyi, Gabor ; Taylor, W. Robert ; Pagano, Patrick J. / NOX and inflammation in the vascular adventitia. In: Free Radical Biology and Medicine. 2009 ; Vol. 47, No. 9. pp. 1254-1266.
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