Genetic determinants of the native collateral circulation (19.3)

Native (pre-existing) collaterals connect adjacent arterial trees and limit ischemic tissue injury. I will review recent findings that collaterals have distinct features, including a unique process of formation and specialized endothelial and smooth muscle cell phenotypes. Moreover, the number and diameter of collaterals (“extent”) in tissues varies widely among different mouse strains and healthy humans, associated with wide differences in the severity of ischemic damage. A single locus, Dce1, is responsible for ~80% of the variation in mouse. Ongoing work is seeking to identify the underlying gene(s) and pathway, and whether this locus links to variation in collateral extent in humans. If so, Dce1 and its up- and down-stream partners could provide markers for collateral abundance to help stratify patients for treatment options, to assess risk-severity before disease occurs, and to provide targets for therapies to stimulate new collateral formation. Recent studies in mice have found that such “neo-collat...