The influence of shear stress on physiological angiogenesis and regression

Hall-Jones, J., Glen, K. E. and Egginton, S. (2008). The influence of shear stress on physiological angiogenesis and regression. In: Proceedings of the Physiological Society.. The Physiological Society 2008 Main Meeting, Cambridge, U. K., (PC90-PC90). 14-16 July 2008.

Author Hall-Jones, J.
Glen, K. E.
Egginton, S.
Title of paper The influence of shear stress on physiological angiogenesis and regression
Conference name The Physiological Society 2008 Main Meeting
Conference location Cambridge, U. K.
Conference dates 14-16 July 2008
Proceedings title Proceedings of the Physiological Society.
Place of Publication London, U. K.
Publisher The Physiological Society
Publication Year 2008
Sub-type Poster
ISSN 1749-6187
Volume 11
Start page PC90
End page PC90
Total pages 1
Language eng
Formatted Abstract/Summary
Chronic vasodilator treatment intensifies levels of shear stress in capillary beds, stimulating a specific form of angiogenesis, termed longitudinal splitting (Egginton, 2001). The use of the α1-adrenoreceptor antagonist, prazosin is well-established for investigation of this process in skeletal muscle (Baum, 2004). Various studies have explored changes in protein expression during shear stress-induced angiogenesis. However, little attention has focussed on the physiological response to cessation of vasodilator treatment and subsequent regression. Male mice, of the C57BL/10 strain, received prazosin dissolved in tap water (50mg/L) for a period of 4 weeks. In addition to control animals, time points were considered during prazosin treatment (14, 28 days) and the regression phase (3, 7, 14, 28, 42 days; n=4). At sampling, the tibialis anterior muscles were removed, following stunning and cervical dislocation. Assessment of capillary-to-fibre was used to confirm the microvascular response. Angiogenesis was demonstrated by a 15% increase in capillarity after 4 weeks of vasodilator treatment. Upon cessation of treatment, an equivalent decrease represented vessel regression. Changes in protein expression were explored using immunoblotting, with membranes being protein-stained to ensure equal loading of samples. ANOVA was used to assess statistical significance. Interestingly, VEGF levels were seen to decline in response to increases in shear stress, with statistical significance seen (P<0.01), supporting the theory of hyperperfusion (Baum, 2004). Despite this decrease, angiogenesis occurred, reinforcing the suggested role of nitric oxide as an angiogenic factor (Williams, 2006). As expected, increases in eNOS levels were seen in response to prazosin treatment. A mirroring decline from peak eNOS levels was seen during the regression phase, reaching significance after 6 weeks (P<0.05). The expression of the main angiogenic VEGF receptor, Flk-1, increased with shear stress, perhaps compensating for reduced levels of its ligand. Interestingly, Ang-2 levels increased bimodally reflecting its pleiotropic effects, with a 23% increase seen after 2 weeks of prazosin treatment. Following a brief decrease, a further 74% increase occurred during vessel regression. The effects of this cytokine were clearly dependent on associated levels of VEGF. We conclude that this form of angiogenesis involves both a rapid phase on induction and regression following withdrawal of stimulus. All procedures follow current UK legislation
Subjects 0606 Physiology
Keyword Shear stress
Q-Index Code EX
Q-Index Status Provisional Code
Institutional Status Unknown
Additional Notes Published under "Communications : Microvascular & Endothelial Physiology : Poster Communication 90"

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Created: Thu, 18 Feb 2010, 09:44:14 EST by Gerald Martin on behalf of Faculty of Science