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Trans-NIH Angiogenesis Workshop; May 20-21, 2013
  • Abstracts

    Genetic determinants of the collateral circulation

    James E. Faber, PhD  [ View bio ]
    (University of North Carolina, Chapel Hill, NC)

    I will review evidence that the collateral circulation is made up of a unique and rare type of vessel (collateral anastomoses), compared to vessels of the general arterio-venous circulation, and that the number and diameter of collaterals in brain, heart, lower extremities, intestine and other tissues varies widely among healthy mice (45-fold) and humans, with a major effect on severity of tissue injury in occlusive vascular diseases. We are trying to determine the genetic and environmental factors responsible for this variation. In mice, we have identified a single polymorphic locus, Candrq1, that is responsible for 70% of the variation. Ongoing work is directed at identifying the underlying gene and pathway. This includes the soon-to-begin Genetic Determinants of Collateral Status in Stroke (GENEDCSS) study to determining if Candrq1 or a related variant is causally linked to variation in collateral status, stroke severity and outcome in patients suffering acute ischemic stroke. Such a variant could provide a genetic marker for collateral abundance to help stratify patients for treatment options and risks. The gene and the pathway it drives could also provide targets for therapies to stimulate new collateral formation in stroke, MI and peripheral artery disease. Recent evidence for such "therapeutic collaterogenesis" in acute MI will be presented. Besides genetic factors, we are also finding that "environmental " factors, ie, aging and other cardiovascular risk factors, cause loss of collateral vessels, resulting in more severe ischemic injury in models of arterial obstruction. Ongoing studies seek to determine the mechanism for this rarefaction and identify strategies to prevent it. Opportunities and challenges for the future regarding the role of the collateral circulation in ischemia will also be discussed.

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Workshop Organizer: NIH

NCI:Nancy Emenaker, PhD, RD
Suzanne Forry-Schaudies, PhD
NHLBI:Yunling Gao, MD, PhD
NIDDK: Teresa Jones, MD

NIH - National Institutes of Health: Turning Discovery Into Health

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