A proposal linking clearance of circulating lipoproteins to tissue metabolic activity as a basis for understanding atherogenesis.

Wolinsky, Harvey

doi:10.1161/01.res.47.3.301

Cited by 143 publications

(63 citation statements)

References 75 publications

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“…All of the thrombomodulin antigen remained in the supernatant, indicating that the material is actually soluble. (14). If the average content of thrombomodulin is 40,000 molecules/cell as we find on cultured umbilical vein endothelial cells (5), then the total content ofthrombomodulin in endothelium is -300 mg.…”

Section: Resultsmentioning

confidence: 86%

Thrombomodulin is present in human plasma and urine.

Ishii¹,

Majerus²

1985

J. Clin. Invest.

293

156

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Thrombomodulin is an endothelial cell membrane protein that is a cofactor required for the rapid activation of plasma protein C. We now report that plasma and urine of normal subjects contains a modified form of thrombomodulin that is soluble. The levels measured by radioimmunoassay were 292±60 ng thrombomodulin/ml plasma and 102±38 ng thrombomodulin/ml urine. Thrombomodulin was isolated from both plasma and urine by immunoaffinity chromatography using a polyclonal anti-human thrombomodulin IgG column. The

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Section: Resultsmentioning

confidence: 86%

Thrombomodulin is present in human plasma and urine.

Ishii¹,

Majerus²

1985

J. Clin. Invest.

293

156

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“…However, LeTx has been shown to induce vascular leakage in experimental models and from clinical data (1, 5-7, 12, 17). Endothelial cells line the entire vascular tree in the human body, covering Ϸ100 m 2 of surface area (49), making it an important potential target for anthrax action. The VEGFRs are preferentially expressed on the surface of endothelial cells, and are master regulators of endothelial cell growth, survival, and permeability throughout the life of an organism, in normal physiology, and in disease (22,50).…”

Section: Discussionmentioning

confidence: 99%

Anthrax lethal toxin induces cell death-independent permeability in zebrafish vasculature

Bolcome

Sullivan

Zeller

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Vascular dysfunction has been reported in human cases of anthrax, in mammalian models of Bacillus anthracis, and in animals injected with anthrax toxin proteins. To examine anthrax lethal toxin effects on intact blood vessels, we developed a zebrafish model that permits in vivo imaging and evaluation of vasculature and cardiovascular function. Vascular defects monitored in hundreds of embryos enabled us to define four stages of phenotypic progression leading to circulatory dysfunction. We demonstrated increased endothelial permeability as an early consequence of toxin action by tracking the extravasation of fluorescent microspheres in toxin-injected embryos. Lethal toxin did not induce a significant amount of cell death in embryonic tissues or blood vessels, as shown by staining with acridine orange, and endothelial cells in lethal toxin-injected embryos continued to divide at the normal rate. Vascular permeability is strongly affected by the VEGF/ vascular permeability factor (VPF) signaling pathway, and we were able to attenuate anthrax lethal toxin effects with chemical inhibitors of VEGFR function. Our study demonstrates the importance of vascular permeability in anthrax lethal toxin action and the need for further investigation of the cardiovascular component of human anthrax disease.endothelial ͉ vascular permeability ͉ VEGF

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“…42 In addition, vWF is thought to increase prothrombotic and procoagulant activity. 8 These markers are synthesized by endothelial cells, 8 and the microvascular endothelium, with its large surface area and production capacity (ie, the microvasculature covers 98% of the total vascular surface area), 43 is likely to be the most important determinant of these plasma concentrations. 8 In addition, according to a previously described concept, endothelial dysfunction in large arteries is paralleled by endothelial dysfunction in resistance vessels that contributes to the development of T2DM.…”

Section: Risk Ratio (95% Ci)mentioning

confidence: 99%

Microvascular Dysfunction Is Associated With a Higher Incidence of Type 2 Diabetes Mellitus

Muris

Houben

Schram

et al. 2012

ATVB

103

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Objective-Recent data support the hypothesis that microvascular dysfunction may be a potential mechanism in the development of insulin resistance. We examined the association of microvascular dysfunction with incident type 2 diabetes mellitus (T2DM) and impaired glucose metabolism by reviewing the literature and conducting a meta-analysis of longitudinal studies on this topic. Methods and Results-We searched Medline and Embase for articles published up to October 2011. Prospective cohort studies that focused on microvascular measurements in participants free of T2DM at baseline were included. Pooled relative risks were calculated using random effects models. Thirteen studies met the inclusion criteria for this meta-analysis. These studies focused on T2DM or impaired fasting glucose, not on impaired glucose tolerance. The pooled relative risks for incident T2DM (3846 cases) was 1.25 (95% confidence interval, 1.15; 1.36) per 1 SD greater microvascular dysfunction when all estimates of microvascular dysfunction were combined. In analyses of single estimates of microvascular dysfunction, the pooled relative risks for incident T2DM was 1.49 (1.36; 1.64) per 1 SD higher plasma soluble E-selectin levels; 1.21(1.11; 1.31) per 1 SD higher plasma soluble intercellular adhesion molecule-1 levels; 1.48 (1.03; 2.12) per 1 SD lower response to acetylcholine-mediated peripheral vascular reactivity; 1.18 (1.08; 1.29) per 1 SD lower retinal arteriole-to-venule ratio; and 1.43 (1.33; 1.54) per 1 logarithmically transformed unit higher albumin-to-creatinine ratio. In addition, the pooled relative risks for incident impaired fasting glucose (409 cases) was 1.

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A proposal linking clearance of circulating lipoproteins to tissue metabolic activity as a basis for understanding atherogenesis.

Cited by 143 publications

References 75 publications

Thrombomodulin is present in human plasma and urine.

Thrombomodulin is present in human plasma and urine.

Anthrax lethal toxin induces cell death-independent permeability in zebrafish vasculature

Microvascular Dysfunction Is Associated With a Higher Incidence of Type 2 Diabetes Mellitus

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