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Genetic determinants of the native collateral circulation (19.3)
Author(s) -
Faber James,
Zhang Hua,
Lucitti Jennifer,
Sealock Robert,
Moore Scott
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.19.3
Subject(s) - collateral , collateral circulation , collateral damage , disease , phenotype , medicine , cardiology , biology , gene , genetics , psychology , business , criminology , finance
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‐collateral” formation can be induced to occur rapidly after acute MI, resulting in increased collateral‐dependent flow and reduced infarct volume. Besides genetic factors, “environmental “ factors, ie, aging and other cardiovascular risk factors, cause reduced collateral extent, resulting in more severe ischemic injury. Studies are under way to identify the underlying mechanism and strategies to prevent it.