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Notch signaling in vascular smooth muscle cells is required to pattern the cerebral vasculature

Aaron Proweller1, Alex C Wright, Debra Horng

  • 1Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Proceedings of the National Academy of Sciences of the United States of America
|October 3, 2007
PubMed

Insights

Notch signaling in vascular smooth muscle cells is crucial for forming the circle of Willis (CW) and preventing stroke. Its deficiency leads to impaired cerebral blood flow and severe neurological deficits.

Area of Science:

  • Neuroscience
  • Vascular Biology
  • Developmental Biology

Background:

  • Stroke is a leading cause of death and disability.
  • Adequate cerebral collateral circulation, particularly the circle of Willis (CW), is vital for preventing ischemic stroke.
  • The genetic factors governing CW formation remain largely unknown.

Purpose of the Study:

  • To investigate the role of Notch signaling in vascular smooth muscle cells (vSMCs) in the development of the cerebral vasculature.
  • To determine the impact of impaired Notch signaling on cerebrovascular function and stroke susceptibility.

Main Methods:

  • Characterization of a mouse model with Notch signaling ablated in vSMCs.
  • Unilateral carotid artery ligation to induce reduced cerebral blood flow.
  • High-resolution microcomputed tomographic (micro-CT) imaging of cerebrovasculature.

Main Results:

  • Mice lacking Notch signaling in vSMCs exhibited intolerance to reduced cerebral blood flow, succumbing to unilateral carotid artery ligation.
  • Carotid ligation led to significantly diminished perfusion in the ipsilateral cerebral hemisphere, indicating anastomotic deficiency.
  • Micro-CT imaging revealed interrupted CW formation and deformed cerebral arteries in these mice.

Conclusions:

  • Notch signaling in vSMCs plays an essential, cell-autonomous role in the patterning and collateral formation of the cerebral arterial circulation.
  • Deficiencies in Notch signaling may contribute to the anatomical defects underlying cerebrovascular accidents like stroke.

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