Department of Cell Biology and Physiology, McAllister Heart Institute, University of North Carolina, 6309 MBRB, Chapel Hill, NC, 27599-7545, USA.
Transl Stroke Res. 2019 Apr;10(2):189-203. doi: 10.1007/s12975-018-0626-y. Epub 2018 Mar 27.
Variation in blood flow mediated by the posterior communicating collateral arteries (PComs) contributes to variation in the severity of tissue injury in obstructive disease. Evidence in animals and humans indicates that differences in the extent of PComs, i.e., their anatomic lumen diameter and whether they are present bilaterally, unilaterally, or absent, are a major factor. These differences arise during development since they are present at birth. However, the causal mechanisms are unknown. We used angiography after maximal dilation to examine involvement of genetic, environmental, and stochastic factors. The extent of PComs varied widely among seven genetically diverse strains of mice. Like pial collaterals in the microcirculation, aging and hypertension reduced PCom diameter, while in contrast, obesity, hyperlipidemia, metabolic syndrome, and diabetes mellitus had no effect. Naturally occurring intrauterine growth restriction had no effect on extent of PCom or pial collaterals in the adult. The number and diameter of PComs evidenced much larger apparent stochastic-dependent variation than pial collaterals. In addition, both PComs underwent flow-mediated outward remodeling after unilateral permanent MCA occlusion that varied with genetic background and was greater on the ipsilesional side. These findings indicate that variation in the number and diameter of PCom collateral arteries arises from stochastic factors and naturally occurring genetic variants that differ from those that cause variation in pial collateral arterioles. Environmental factors also contribute: aging and hypertension reduce PCom diameter. Our results suggest possible sources of variation of PComs in humans and provide information relevant when studying mouse models of occlusive cerebrovascular disease.
后交通动脉（PCom）介导的血流变化导致阻塞性疾病中组织损伤程度的变化。动物和人类的证据表明，PCom 的程度差异，即其解剖管腔直径以及它们是否双侧、单侧或不存在，是一个主要因素。这些差异是在发育过程中产生的，因为它们在出生时就存在。然而，因果机制尚不清楚。我们使用最大扩张后的血管造影检查遗传、环境和随机因素的参与情况。七种遗传多样性的小鼠品系之间 PCom 的程度差异很大。与微循环中的软脑膜侧支一样，衰老和高血压会降低 PCom 直径，而肥胖、高脂血症、代谢综合征和糖尿病则没有影响。自然发生的宫内生长受限对成年 PCom 或软脑膜侧支的程度没有影响。PCom 的数量和直径表现出比软脑膜侧支更大的明显随机依赖性变异性。此外，单侧永久性 MCA 闭塞后 PCom 经历了血流介导的向外重塑，这种重塑与遗传背景有关，在同侧侧更为明显。这些发现表明，PCom 侧支动脉数量和直径的变化来自随机因素和自然发生的遗传变异，这些变异与引起软脑膜侧支小动脉变化的因素不同。环境因素也有贡献：衰老和高血压会降低 PCom 直径。我们的结果提示了人类 PCom 变化的可能来源，并为研究阻塞性脑血管病的小鼠模型提供了相关信息。
