Genetic and Environmental Contributions to Variation in the Posterior Communicating Collaterals of the Circle of Willis
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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.
KeywordsCollateral circulation Posterior communicating artery Circle of Willis Genetics Hypertension Aging
Anterior cerebral artery
Circle of Willis
Cardiovascular and stroke risk factors
Embryonic day 1(2,3…etc)
Internal carotid artery
Middle cerebral artery
Permanent proximal M2-MCA occlusion P1 postnatal day 1(2,3…etc)
Posterior cerebral artery
Posterior communicating collateral artery
Renin overexpressing transgenic mouse model of hypertension
Small for gestational age
The sources of funding are the National Institutes of Health and National Institute of Neurological Diseases and Stroke grant NS083633.
JF designed the study and figures and wrote the manuscript. HZ performed angiography, pMCAO, pial collateral morphometry, statistical analysis, animal husbandry, and finalized the figures. WR, KD, BS, CB, and SH performed the morphometry of PComs and primary cerebral arteries and statistical analysis.
This study was funded by the National Institutes of Health and National Institute of Neurological Diseases and Stroke grant NS083633.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.
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