| ironjustice@aol.com 2006-05-08, 6:26 pm |
| Departement f=FCr Veterin=E4rphysiologie und Tierern=E4hrung > Institut
f=FCr Veterin=E4rphysiologie > Max Gassmann
Gassmann
Current Research Project
Title / Titel Effect of chronic excessive erythrocytosis on vascular
function: endothelial dysfunction and inflammation Summary /
ZusammenfassungExcessive erythrocytosis and elevated blood volume
result in severely increased blood viscosity and reduced blood velocity
that may have significant detrimental effects on morphology and
ultimately function of the vascular endothelium. Since blood brain
barrier stability is crucial for normal physiological function, we are
investigating the effect of excessive erythrocytosis on vascular
development and function. We have used our previously characterised
Epo-overexpressing transgenic mouse line (termed tg6) that has a
hematocrit of 0.8-0.9 and significantly reduced life span, the cause of
which is still unidentified. These mice have abnormally high levels of
nitric oxide (NO) a potent pro-inflammatory molecule, suggesting
altered vascular permeability and function. We observed that in 4-5
month old tg6 mice, brain vessel density was reduced (16%) and vessel
diameter significantly increased (15%) compared to wt. Interestingly,
no significant increases in vascular permeability under normoxic or
acute hypoxic conditions (8% O2, 4h) were detected although the number
of tight junction proteins per blood vessel were increased indicating
existence of compensatory mechanisms enabling normal vascular function
despite excessive erythrocytosis. Notably, electron microscopy analysis
revealed that tg6 endothelium has altered morphological characteristics
reminiscent of ongoing inflammatory processes. Thus chronic excessive
erythrocytosis alters normal vascular characteristics and may
ultimately affect blood brain barrier function and susceptibility to
injury. We are now continuing this work by investigating the effect of
chronic excessive erythrocytosis on aged mice (9-11 months old) to see
the long term effects of high hematocrit on vascular integrity.
Particular emphasis is placed on the role of inflammatory molecules on
endothelial survival and matrix deposition. Furthermore the role of
free radicals will also be studied. This work will play provide
instrumental information not only for treatment of individuals
suffering from this chronic disease but also for patients that are
treated long term with human recombinant Epo, and athletes that use Epo
as a doping agent.Publications / PublikationenKatja Heinicke, Oliver
Baum, Omolara O. Ogunshola, Johannes Vogel, Thomas Stallmach, David P.
Wolfer, Stephan Keller, Klaus Weber, Peter D. Wagner, Max Gassmann, and
Valentin Djonov. Excessive erythrocytosis in adult mice overexpressing
erythropoietin leads to hepatic, renal, neuronal and muscular
degeneration. Submitted.
Ogunshola OO, Djonov V, Staudt R, Vogel J, Gassmann M. Chronic
excessive erythrocytosis induces endothelial activation and damage in
mouse brain. Am J Physiol Regul Integr Comp Physiol. 2006
Mar;290(3):R678-84. Epub 2005 Oct 27.
Keywords / SuchbegriffeErythropoietin, vascular permeability,
inflammation, hypoxiaProject Leadership and Contacts
Projektleitung und KontakteProf. Dr. Max Gassmann (Project Leader)
maxg@access.unizh.ch
Dr. Omolara Ogunshola larao@access.unizh.ch
Funding Source(s)
Unterst=FCtzt durchSNF (Personen- und Projektf=F6rderung)
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