Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, NC, USA.
J Mol Cell Cardiol. 2010 Aug;49(2):251-9. doi: 10.1016/j.yjmcc.2010.03.014. Epub 2010 Mar 25.
The native (pre-existing) collateral circulation minimizes tissue injury if obstructive vascular disease develops. Evidence suggests that large differences in collateral extent exist among healthy individuals, presumably from as-yet unknown genetic and/or environmental factors. Little is known regarding when or how native collaterals form-information needed to identify these factors. We examined collateral development between the middle and anterior cerebral artery trees in BALB/c and C57BL/6 mouse embryos-strains with marked differences in adult collateral density and diameter (85% fewer, 50% smaller in BALB/c). The circulation was dilated, fixed and stained. By E15.5, a "primary collateral plexus" was beginning to form in both strains. By E18.5, plexus vessel number peaked but was 60% less and diameter smaller in BALB/c (P<0.001). Earlier time points were examined to determine if these differences correlated with differences in patterning of the general circulation. At approximately E9.0, the primary capillary plexus was similar between strains, but by E12.5 branching was less and diameter larger in BALB/c (P<0.05). Between E12.5-E18.5-during pial artery tree development-small differences in tree size, branch number and distance between branches did not correlate with the large difference in collaterogenesis. Pruning of nascent collaterals between P1-P21 was comparable in both strains, yielding the adult density, but diameter and tortuosity increased less in BALB/c. Pericyte recruitment to nascent collaterals was comparable, despite lower VEGF-A and PDGF-B expression in BALB/c mice. These findings demonstrate that collaterals form late during vascular development and undergo postnatal maturation and that differences in genetic background have dramatic effects on these processes.
如果阻塞性血管疾病发展，固有（预先存在的）侧支循环将使组织损伤最小化。有证据表明，健康个体之间的侧支扩展程度存在很大差异，这可能归因于尚未知的遗传和/或环境因素。关于固有侧支如何形成，即形成这些因素的信息，人们知之甚少。我们检查了 BALB/c 和 C57BL/6 两种品系的胚胎鼠大脑中动脉和前脑动脉之间的侧支发育情况——这两种品系在成年时的侧支密度和直径上存在显著差异（BALB/c 中的侧支数量减少 85%，直径减少 50%）。我们扩张、固定并染色了循环系统。到 E15.5 时，两种品系都开始形成“初级侧支丛”。到 E18.5 时，侧支丛的血管数量达到峰值，但 BALB/c 的数量减少了 60%，直径更小（P<0.001）。我们检查了更早的时间点，以确定这些差异是否与总体循环模式的差异有关。大约在 E9.0 时，两种品系的初级毛细血管丛相似，但到 E12.5 时，BALB/c 的分支较少，直径较大（P<0.05）。在 E12.5-E18.5 期间，在软脑膜动脉树发育过程中，树大小、分支数量和分支之间的距离的微小差异与侧支生成的巨大差异无关。在两种品系中，新生侧支的修剪在 P1-P21 之间是相似的，产生了成年密度，但 BALB/c 的直径和扭曲度增加较少。尽管 BALB/c 小鼠的 VEGF-A 和 PDGF-B 表达较低，但新生侧支的周细胞募集是相似的。这些发现表明，侧支在血管发育后期形成，并在出生后成熟，而遗传背景的差异对这些过程有显著影响。
