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Angiopoietin/Tie2 pathway mediates type 2 diabetes induced vascular damage after cerebral stroke

Xu Cui1, Michael Chopp, Alex Zacharek

  • 1Department of Neurology, Henry Ford Hospital, Detroit, MI 48202, USA.

Neurobiology of Disease
|April 26, 2011
PubMed

Insights

Type-2 diabetes exacerbates stroke-induced brain vascular damage by increasing hemorrhage and blood-brain barrier leakage. This is linked to altered Angiopoietin-Tie2 signaling, impacting cerebrovascular integrity.

Area of Science:

  • Neuroscience
  • Vascular Biology
  • Metabolic Disorders

Background:

  • Type-2 diabetes mellitus (T2DM) is a growing global health concern.
  • Stroke is a leading cause of death and disability worldwide.
  • The impact of T2DM on cerebrovascular damage following stroke remains incompletely understood.

Purpose of the Study:

  • To investigate the effects of T2DM on cerebral vascular damage after stroke.
  • To elucidate the molecular mechanisms underlying diabetes-induced cerebrovascular injury.

Main Methods:

  • Transient middle cerebral artery occlusion (MCAo) model in type-2 diabetic (db/db) and wild-type (WT) mice.
  • Assessment of neurological deficits, mortality, hemorrhagic rate, and cerebrovascular parameters.
  • Analysis of blood-brain barrier integrity and expression of Angiopoietin-Tie2 signaling pathway components.
  • In vitro studies using primary mouse brain endothelial cells (MBECs) and common carotid artery (CCA) cultures.

Main Results:

  • T2DM mice exhibited increased hyperglycemia, hemorrhagic rate, mortality, and cerebrovascular density post-stroke.
  • Reduced cerebrovascular diameter, arteriolar density, and arterial mural cell numbers were observed in T2DM mice.
  • Increased blood-brain barrier leakage, elevated Angiopoietin2, and decreased Angiopoietin1 and Tie2 expression in the ischemic brain.
  • In vitro studies showed altered endothelial cell function and impaired artery cell migration in T2DM models.

Conclusions:

  • T2DM significantly worsens cerebral vascular damage after stroke.
  • Decreased Angiopoietin1/Tie2 signaling and increased Angiopoietin2 contribute to diabetes-induced cerebrovascular injury.
  • These findings highlight potential therapeutic targets for stroke in diabetic patients.

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