Nitric oxide and portal hypertension: Interface of vasoreactivity and angiogenesis

Langer, Daniël; Shah, Vijay H.

doi:10.1016/j.jhep.2005.10.004

Cited by 67 publications

(48 citation statements)

References 87 publications

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“…In reciprocal regulation, the SEC NO suppresses stellate cell activation and collagen expression that facilitates fibrosis (16). Loss of NO contributes to pathogenic angiogenesis, fibrosis, and portal hypertension in the liver (39). Peroxynitrite formed from the reaction of superoxide and NO has been proposed as a pathogenic mediator of liver perfusion defects caused by obesity and insulin resistance (21).…”

Section: Discussionmentioning

confidence: 99%

Arsenic-stimulated liver sinusoidal capillarization in mice requires NADPH oxidase–generated superoxide

Straub

Clark²,

Ross³

et al. 2008

J. Clin. Invest.

107

114

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Environmental arsenic exposure, through drinking contaminated water, is a significant risk factor for developing vascular diseases and is associated with liver portal hypertension, vascular shunting, and portal fibrosis through unknown mechanisms. We found that the addition of low doses of arsenite to the drinking water of mice resulted in marked pathologic remodeling in liver sinusoidal endothelial cells (SECs), including SEC defenestration, capillarization, increased junctional PECAM-1 expression, protein nitration, and decreased liver clearance of modified albumin. Furthermore, the pathologic changes observed after in vivo exposure were recapitulated in isolated mouse SECs exposed to arsenic in culture. To investigate the role of NADPH oxidase-generated ROS in this remodeling, we examined the effect of arsenite in the drinking water of mice deficient for the p47 subunit of the NADPH oxidase and found that knockout mice were protected from arsenite-induced capillarization and protein nitration. Furthermore, ex vivo arsenic exposure increased SEC superoxide generation, and this effect was inhibited by addition of a Nox2 inhibitor and quenched by the cellpermeant superoxide scavenger. In addition, inhibiting either oxidant generation or Rac1-GTPase blocked ex vivo arsenic-stimulated SEC differentiation and dysfunction. Our data indicate that a Nox2-based oxidase is required for SEC capillarization and that it may play a central role in vessel remodeling following environmentally relevant arsenic exposures.

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Section: Discussionmentioning

confidence: 99%

Arsenic-stimulated liver sinusoidal capillarization in mice requires NADPH oxidase–generated superoxide

Straub

Clark²,

Ross³

et al. 2008

J. Clin. Invest.

107

114

View full text Add to dashboard Cite

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“…11 Endothelial dysfunction and vasodilation possibly mediated by endocannabinoids and nitric oxide, and altered subendothelial-platelet interaction further impairs hemostasis. 12 However, many of these changes are offset by decreased anticoagulant proteins such as protein C, protein S, protein Z, protein Z-dependent protease inhibitor, antithrombin, heparin cofactor II, and ␣2-macroglobulin, all of which are synthesized by the liver. Levels of tissue factor pathway inhibitor (TFPI) synthesized by endothelial cells are variably reported as normal or decreased in patients with liver failure.…”

Section: Pathophysiology Of Coagulation In Livermentioning

confidence: 99%

Coagulation disorders and hemostasis in liver disease

et al. 2006

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Normal coagulation has classically been conceptualized as a Y-shaped pathway, with distinct "intrinsic" and "extrinsic" components initiated by factor XII or factor VIIa/ tissue factor, respectively, and converging in a "common" pathway at the level of the FXa/FVa (prothrombinase) complex. Until recently, the lack of an established alternative concept of hemostasis has meant that most physicians view the "cascade" as a

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“…29) Multiple lines of evidence suggest that many proinflammatory molecules, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and nitric oxide (NO), directly induce angiogenesis. 30,31) Kupffer cells act not only as phagocytic cells, but also as obligatory regulators of inflammation and fibrosis by producing various cytokines, chemokines, and reactive oxygen and nitrogen species. 32,33) The chemokinedependent accumulation of monocyte-derived macrophages has been identified as an important mechanism for perpetuating hepatic inflammation and promoting fibrogenesis in experimental mouse models and in human liver diseases.…”

Section: Angiogenesis In Liver Fibrosismentioning

confidence: 99%

Differential Roles of Angiogenesis in the Induction of Fibrogenesis and the Resolution of Fibrosis in Liver

Park

Kim

et al. 2015

Biological & Pharmaceutical Bulletin

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Liver fibrosis is a wound healing process that includes inflammation, deposition of extracellular matrix molecules, and pathological neovascularization. Angiogenesis, which is defined by the formation of new blood vessels from pre-existing vessels, is a complex and dynamic process under both physiological and pathological conditions. Although whether angiogenesis can induce or occur in parallel with the progression of hepatic fibrosis has not yet been determined, intrahepatic sinusoidal formation and remodeling are key features of liver fibrosis. Some recent evidence has suggested that experimental inhibition of angiogenesis ameliorates the development of liver fibrosis, while other recent studies indicate that neutralization or genetic ablation of vascular endothelial growth factor (VEGF) in myeloid cells can delay tissue repair and fibrosis resolution in damaged liver. In this review, we briefly summarize the current knowledge about the differential roles of angiogenesis in the induction of fibrogenesis and the resolution of fibrosis in damaged livers. Possible strategies for the prevention and treatment of liver fibrosis are also discussed.

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Nitric oxide and portal hypertension: Interface of vasoreactivity and angiogenesis

Cited by 67 publications

References 87 publications

Arsenic-stimulated liver sinusoidal capillarization in mice requires NADPH oxidase–generated superoxide

Arsenic-stimulated liver sinusoidal capillarization in mice requires NADPH oxidase–generated superoxide

Coagulation disorders and hemostasis in liver disease

Differential Roles of Angiogenesis in the Induction of Fibrogenesis and the Resolution of Fibrosis in Liver

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