title: Excessive erythrocytosis compromises the blood-endothelium interface in erythropoietin-overexpressing mice.
abstract: 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.
authors.affiliation: Department of Physiology and CCR, Charité, Berlin, Germany.
authors.forename: Vincent
authors.initials: V
authors.lastname: Richter
authors.forename: Michele D
authors.initials: MD
authors.lastname: Savery
authors.forename: Max
authors.initials: M
authors.lastname: Gassmann
authors.forename: Oliver
authors.initials: O
authors.lastname: Baum
authors.forename: Edward R
authors.initials: ER
authors.lastname: Damiano
authors.forename: Axel R
authors.initials: AR
authors.lastname: Pries
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004921:Erythropoietin / Q000235:genetics; D006339:Heart Rate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008833:Microcirculation; D018482:Muscle, Skeletal / Q000098:blood supply / Q000502:physiology; D011086:Polycythemia / Q000503:physiopathology*; D014655:Vascular Resistance
chemical_list: D004921:Erythropoietin