Vascular Oxidant Stress Enhances Progression and Angiogenesis of Experimental Atheroma

Khatri, Jaikirshan; Johnson, Craig B.; Magid, Richard; Lessner, Susan M.; Laude, Karine; Dikalov, Sergey; Harrison, David G.; Sung, Hak‐Joon; Yuan, Rong; Galis, Zorina S.

doi:10.1161/01.cir.0000109698.70638.2b

Cited by 207 publications

(140 citation statements)

References 35 publications

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“…For instance, overexpression of the NADPH oxidase subunit, p22 phox has been shown to increase HIF-1a, VEGF expression and intralesional angiogenesis and to promote experimental atheroma progression. 44 Our present data demonstrated that deficiency of the NADPH oxidase p47 phox attenuates Ang-2 expression and blunts angiogenic response in the neointima of DIO mice. Our data also show that leptin-induced Ang-2 expression, as well as cell migration and proliferation are dependent on NADPH oxidase.…”

Section: Disscussionsupporting

confidence: 60%

Critical role of the NADPH oxidase subunit p47phox on vascular TLR expression and neointimal lesion formation in high-fat diet-induced obesity

Chen

Stinnett

2008

Laboratory Investigation

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Reactive oxygen species (ROS) formation is associated with inflammation and vasculature dysfunction. We investigated the potential role of the NADPH oxidase on vascular Toll-like receptor (TLR) expression and carotid neointimal formation in high-fat (HF) diet-induced obesity (DIO) model. Using mice DIO and common carotid artery flow cessation-induced lesion formation models, we examined vascular TLR2 and TLR4 expression and neointimal formation in NADPH oxidase subunit p47 phox -deficient (p47 phox-/-) mice. Feeding C57BL/6J mice an HF diet for 22 weeks resulted in significant increases in p47 phox , TLR2 and TLR4 expression in vascular tissues compared with mice fed a low-fat (LF) diet. Minimal changes in TLR2 and TLR4 expression was detected in p47 phox-/-DIO mice. Furthermore, flow cessation-induced angiogenic and inflammatory response and neointimal formation were significantly attenuated in p47 phoxÀ/À DIO mice compared with wild-type DIO mice. In addition, exposure of endothelial cells to leptin led to ROS formation; this was accompanied by upregulation of TLR2, TLR4 expression and its downstream signaling. Leptin also increased endothelial cell migration and proliferation. Pharmacological inhibition of NADPH oxidase or genetic deletion of p47 phox significantly diminished these alterations. Obesity increases neointimal formation via a mechanism involving p47 phox -TLRs signaling, suggesting that the NADPH oxidase may represent a potential novel therapeutic target for the treatment of obesity-associated vascular inflammation and dysfunction.

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Section: Disscussionsupporting

confidence: 60%

Critical role of the NADPH oxidase subunit p47phox on vascular TLR expression and neointimal lesion formation in high-fat diet-induced obesity

Chen

Stinnett

2008

Laboratory Investigation

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“…In VSMC, therefore, insulin activates the HIF-1/VEGF pathway, which is deeply involved in new blood vessel formation [18], thus mimicking the action of hypoxia [19][20][21][22][23].…”

Section: Discussionmentioning

confidence: 99%

Insulin activates hypoxia-inducible factor-1α in human and rat vascular smooth muscle cells via phosphatidylinositol-3 kinase and mitogen-activated protein kinase pathways: impairment in insulin resistance owing to defects in insulin signalling

et al. 2006

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“…In addition, the combination of inactivation of NO • by O 2 •− and increased production of the endothelial hyperpolarizing factor H 2 O 2 leads to impaired vasodilation (Bauersachs et al 1996). The balance between endothelial proliferation and apoptosis is also altered by ROS, which can lead to excessive angiogenesis (Khatri et al 2004) or loss of endothelial cells (Lin et al 2004). All of these consequences contribute to the pathophysiology of the response to injury.…”

Section: Endothelial Dysfunctionmentioning

confidence: 99%

Basic Mechanisms of Oxidative Stress and Reactive Oxygen Species in Cardiovascular Injury

Papaharalambus

Griendling

2007

Trends in Cardiovascular Medicine

290

224

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The development of vascular disease has its origins in an initial insult to the vessel wall by biological or mechanical factors. The disruption of homeostatic mechanisms leads to alteration of the original architecture of the vessel and its biological responsiveness, contributing to acute or chronic diseases such as stroke, hypertension and atherosclerosis. Endothelial dysfunction, macrophage infiltration of the vessel wall, and proliferation and migration of smooth muscle cells all involve different types of reactive oxygen species, produced by various vessel wall components. Although basic science and animal research have clearly established the role of reactive oxygen species in the progression of vascular disease, the failure of clinical trials with antioxidant compounds has underscored the need for better antioxidant therapies and a more thorough understanding of the role of reactive oxygen species in cardiovascular physiology and pathology.The fundamental processes underlying the development of vascular diseases such as atherosclerosis, restenosis and hypertensive vascular remodeling have their origins in an initial insult to the vessel wall. Such an insult may arise from mechanical disruption that occurs during percutaneous coronary angioplasty or at regions of oscillatory shear stress, or it can result from biological causes, such as hypercholesterolemia, excess free radicals, diabetes, increased concentrations of plasma homocysteine, or infectious agents. Injury promotes disruption of the homeostatic mechanisms of the endothelial protective barrier, changing its natural properties, increasing its adhesiveness to leukocytes and altering its permeability. This endothelial dysfunction also leads to the formation of vasoactive molecules, which in turn induce inflammatory genes, inactivate nitric oxide (NO • ) and its protective functions, and activate matrix metalloproteinases, leading to extracellular matrix remodeling, and increased smooth muscle cell (VSMC) growth, migration and proliferation. Each of these processes contributes to thickening of the vessel wall or the formation of lesions that can lead to hypertension, acute myocardial infarction and stroke. Reactive Oxygen Species and Vascular InjuryIn the past decade a staggering amount of evidence implicates a common denominator, reactive oxygen species (ROS), in the development of most cardiovascular diseases (Figure 1). Superoxide (O 2 •− ) and hydrogen peroxide (H 2 O 2 ) are two of the most biologically important ROS in the cardiovascular system, and are produced in vascular cells by a number of oxidases, including the NADPH oxidases (Nox) and xanthine oxidase, lipoxygenases, cytochrome p450,

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Vascular Oxidant Stress Enhances Progression and Angiogenesis of Experimental Atheroma

Abstract: Background-Although multiple pathological processes have been associated with oxidative stress, the causative relation between oxidative stress and arterial lesion progression remains unclear.

Cited by 207 publications

References 35 publications

Critical role of the NADPH oxidase subunit p47phox on vascular TLR expression and neointimal lesion formation in high-fat diet-induced obesity

Critical role of the NADPH oxidase subunit p47phox on vascular TLR expression and neointimal lesion formation in high-fat diet-induced obesity

Insulin activates hypoxia-inducible factor-1α in human and rat vascular smooth muscle cells via phosphatidylinositol-3 kinase and mitogen-activated protein kinase pathways: impairment in insulin resistance owing to defects in insulin signalling

Basic Mechanisms of Oxidative Stress and Reactive Oxygen Species in Cardiovascular Injury

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