Genetic architecture underlying variation in extent and remodeling of the collateral circulation.
Genetic architecture underlying variation in extent and remodeling of the collateral circulation.
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DOI：
10.1161/circresaha.110.224634
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发表时间：
2010-08-20
影响因子：
20.1
通讯作者：
Faber JE
中科院分区：
文献类型：
--
作者：
Wang S;Zhang H;Dai X;Sealock R;Faber JE
Collaterals are arteriole-to-arteriole anastomoses that connect adjacent arterial trees. They lessen ischemic tissue injury by serving as endogenous bypass vessels when the trunk of one tree becomes narrowed by vascular disease. The number and diameter (“extent”) of native (pre-existing) collaterals, plus their amount of lumen enlargement (growth/remodeling) in occlusive disease, show remarkably wide variation among inbred mouse strains (eg, C57BL/6 and BALB/c), resulting in large differences in tissue injury in models of occlusive disease. Evidence suggests similar large differences exist among healthy humans. To identify candidate loci responsible for genetic-dependent collateral variation. Cerebral collateral number and diameter were determined in 221 C57BL/6-x-BALB/c F2 progeny, followed by linkage analysis to identify quantitative trait loci (QTL) for collateral number and diameter. Four QTL were obtained for collateral number, including epistasis between two loci. A QTL that was identical to the strongest QTL for collateral number on chromosome 7 (LOD=29, effect size=37%) was also mapped for collateral diameter (LOD=17, effect size=30%). Chromosome substitution strain analysis confirmed this locus. We also obtained a unique QTL on chromosome 11 for collateral remodeling after middle cerebral artery occlusion. Association mapping within the chromosome 7 QTL interval using collateral traits measured for 15 inbred strains, delineated 172k (p=0.00002) and 290k (p=0.0004) base-pair regions on chromosome 7 containing 2 and 9 candidate genes, respectively. We conclude that collateral extent and remodeling are unique, highly heritable complex traits, with one QTL predominantly affecting native collateral number and diameter.
