Growing collateral arteries on demand

Charles C. Oh, Jason D. Klein, Raymond Q. Migrino, Kent L. Thornburg

    Research output: Contribution to journalArticle

    2 Scopus citations

    Abstract

    Recent studies have significantly advanced our understanding of arteriogenesis, raising hope that therapies to increase collateral arterial formation may become important new tools in the treatment of ischemic disease. The most important initiating trigger for arteriogenesis is the marked increase in shear stress which is sensed by the endothelium and leads to characteristic changes. Intracellularly, it was shown that platelet endothelial cell adhesion molecule (PECAM-1) becomes tyrosine-phosphorylated in response to increased shear stress, suggesting a role as a possible mechanoreceptor for dynamic and continual monitoring of shear stress. The signal generated by PECAM-1 leads to the activation of the Rho pathway among others. More than 40 genes have been shown to have a shear stress responsive element. The Rho pathway is activated early and appears to be essential to the arteriogenic response as inhibiting it abolished the effect of fluid shear stress. Overexpression of a Rho pathway member, Actin-binding Rho protein (Abra), led to a 60% increase in collateral perfusion over simple femoral artery occlusion. A patent for the Abra gene has been filed recently. It may be a harbinger of a future where collateral arteries grown on demand may become an effective treatment for ischemic vascular disease.

    Original languageEnglish (US)
    Pages (from-to)189-198
    Number of pages10
    JournalRecent Patents on Cardiovascular Drug Discovery
    Volume6
    Issue number3
    StatePublished - Sep 1 2011

    Keywords

    • Arteriogenesis
    • Collateral artery
    • Mechanotransduction
    • Shear stress

    ASJC Scopus subject areas

    • Drug Discovery
    • Cardiology and Cardiovascular Medicine
    • Pharmacology (medical)

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