ORIGINAL ARTICLE Genetic and Environmental Contributions to Variation in the Posterior Communicating Collaterals of the Circle of Willis James E. Faber 1 & Hua Zhang 1 & Wojciech Rzechorzek 1 & Kathy Z. Dai 1 & Benjamin T. Summers 1 & Cooper Blazek 1 & Samuel J. Hedges 1 Received: 17 January 2018 /Revised: 14 March 2018 /Accepted: 16 March 2018 # Springer Science+Business Media, LLC, part of Springer Nature 2018 Abstract 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 sug- gest possible sources of variation of PComs in humans and provide information relevant when studying mouse models of occlusive cerebrovascular disease. Keywords Collateral circulation . Posterior communicating artery . Circle of Willis . Genetics . Hypertension . Aging Abbreviations ACA Anterior cerebral artery BA Basilar artery CoW Circle of Willis CSRFs Cardiovascular and stroke risk factors E1 Embryonic day 1(2,3…etc) ICA Internal carotid artery MCA Middle cerebral artery pMCAO Permanent proximal M2-MCA occlusion P1 post- natal day 1(2,3…etc) PCA Posterior cerebral artery PCom Posterior communicating collateral artery RTG Renin overexpressing transgenic mouse model of hypertension SGA Small for gestational age WT Wildtype strain Introduction The circle of Willis (CoW) is a specialized network created by three collateral arteries, the anterior communicating artery (ACom) and the bilateral posterior communicating arteries (PComs) that interconnect the internal carotid arteries (ICAs) and basilar artery (BA) via the proximal trunks of the anterior and posterior cerebral arteries. Physiologically, the CoW has Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12975-018-0626-y) contains supplementary material, which is available to authorized users. * James E. Faber jefaber@med.unc.edu 1 Department of Cell Biology and Physiology, McAllister Heart Institute, University of North Carolina, 6309 MBRB, Chapel Hill, NC 27599-7545, USA Translational Stroke Research https://doi.org/10.1007/s12975-018-0626-y