Chronic excessive erythrocytosis induces endothelial activation and damage in mouse brain

Ogunshola, O O; Djonov, V; Staudt, R; Vogel, J; Gassmann, M (2006). Chronic excessive erythrocytosis induces endothelial activation and damage in mouse brain. American journal of physiology - regulatory, integrative and comparative physiology, 290(3), R678-84. Bethesda, Md.: American Physiological Society 10.1152/ajpregu.00246.2005

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Excessive erythrocytosis results in severely increased blood viscosity, which may have significant detrimental effects on endothelial cells and, ultimately, function of the vascular endothelium. Because blood-brain barrier stability is crucial for normal physiological function, we used our previously characterized erythropoietin-overexpressing transgenic (tg6) mouse line (which has a hematocrit of 0.8-0.9) to investigate the effect of excessive erythrocytosis on vessel number, structure, and integrity in vivo. These mice have abnormally high levels of nitric oxide (NO), a potent proinflammatory molecule, suggesting altered vascular permeability and function. In this study, we observed that brain vessel density of tg6 mice was significantly reduced (16%) and vessel diameter was significantly increased (15%) compared with wild-type mice. Although no significant increases in vascular permeability under normoxic or acute hypoxic conditions (8% O2 for 4 h) were detected, electron-microscopic analysis revealed altered morphological characteristics of the tg6 endothelium. Tg6 brain vascular endothelial cells appeared to be activated, with increased luminal protrusions reminiscent of ongoing inflammatory processes. Consistent with this observation, we detected increased levels of intercellular adhesion molecule-1 and von Willebrand factor, markers of endothelial activation and damage, in brain tissue. We propose that chronic excessive erythrocytosis and sustained high hematocrit cause endothelial damage, which may, ultimately, increase susceptibility to vascular disease.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy

UniBE Contributor:

Djonov, Valentin

ISSN:

0363-6119

ISBN:

16254128

Publisher:

American Physiological Society

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:49

Last Modified:

17 Mar 2015 21:49

Publisher DOI:

10.1152/ajpregu.00246.2005

PubMed ID:

16254128

Web of Science ID:

000235210300025

URI:

https://boris.unibe.ch/id/eprint/20358 (FactScience: 3646)

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