Genetic and Environmental Contributions to Variation in the Posterior Communicating Collaterals of the Circle of Willis

  • James E. Faber
  • Hua Zhang
  • Wojciech Rzechorzek
  • Kathy Z. Dai
  • Benjamin T. Summers
  • Cooper Blazek
  • Samuel J. Hedges
Original Article
  • 17 Downloads

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 suggest 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 postnatal 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

Notes

Acknowledgements

The sources of funding are the National Institutes of Health and National Institute of Neurological Diseases and Stroke grant NS083633.

Author Contributions

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.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

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.

Supplementary material

12975_2018_626_MOESM1_ESM.pptx (362 kb)
ESM 1 (PPTX 361 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • 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
  1. 1.Department of Cell Biology and Physiology, McAllister Heart InstituteUniversity of North CarolinaChapel HillUSA

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