Excessive erythrocytosis compromises the blood-endothelium interface in erythropoietin-overexpressing mice

Richter, Vincent; Savery, Michele D; Gassmann, Max; Baum, Oliver; Damiano, Edward R; Pries, Axel R (2011). Excessive erythrocytosis compromises the blood-endothelium interface in erythropoietin-overexpressing mice. Journal of physiology, 589(Pt 21), pp. 5181-92. Oxford: Wiley-Blackwell 10.1113/jphysiol.2011.209262

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Elevated systemic haematocrit (Hct) increases risk of cardiovascular disorders, such as stroke and myocardial infarction. One possible pathophysiological mechanism could be a disturbance of the blood-endothelium interface. It has been shown that blood interacts with the endothelial surface via a thick hydrated macromolecular layer (the 'glycocalyx', or 'endothelial surface layer'--ESL), modulating various biological processes, including inflammation, permeability and atherosclerosis. However, the consequences of elevated Hct on the functional properties of this interface are incompletely understood. Thus, we combined intravital microscopy of an erythropoietin overexpressing transgenic mouse line (tg6) with excessive erythrocytosis (Hct 0.85), microviscometric analysis of haemodynamics, and a flow simulation model to assess the effects of elevated Hct on glycocalyx/ESL thickness and flow resistance. We show that the glycocalyx/ESL is nearly abolished in tg6 mice (thickness: wild-type control: 0.52 μm; tg6: 0.13 μm; P < 0.001). However, the corresponding reduction in network flow resistance contributes <20% to the maintenance of total peripheral resistance observed in tg6 mice. This suggests that the pathological effects of elevated Hct in these mice, and possibly also in polycythaemic humans, may relate to biological corollaries of a reduced ESL thickness and the consequent alteration in the blood-endothelium interface, rather than to an increase of flow resistance.

Item Type:

Journal Article (Original Article)

Division/Institute:

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

UniBE Contributor:

Baum, Oliver

ISSN:

0022-3751

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:17

Last Modified:

13 Jan 2016 16:23

Publisher DOI:

10.1113/jphysiol.2011.209262

PubMed ID:

21859826

Web of Science ID:

000296369000016

URI:

https://boris.unibe.ch/id/eprint/5117 (FactScience: 209835)

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