Vascular protection by angiotensin receptor antagonism involves differential vegf expression in both hemispheres after experimental stroke

Weihua Guan, Payaningal R. Somanath, Anna Koza, Anna Goc, Azza B. El-Remessy, Adviye Ergul, Maribeth H. Johnson, Ahmed Alhusban, Sahar Soliman, Susan C. Fagan

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

We identified that the angiotensin receptor antagonist, candesartan, has profound neurovascular protective properties when administered after ischemic stroke and was associated with a proangiogenic state at least partly explained by vascular endothelial growth factor A (VEGFA). However, the spatial distribution of vascular endothelial growth factor (VEGF) isoforms and their receptors remained unknown. Protein analysis identified a significant increase in vascular endothelial grow factor B (VEGFB) in the cerebrospinal fluid (CSF) and the ischemic hemispheres (with increased VEGF receptor 1 activation) of treated animals (p<0.05) which was co-occurring with an increase in protein kinase B (Akt) phosphorylation (p<0.05). An increase in VEGFA protein in the contralesional hemisphere corresponded to a significant increase in vascular density at seven days (p<0.01) after stroke onset. Vascular restoration by candesartan after stroke maybe related to differential regional upregulation of VEGFB and VEGFA, promoting a "prosurvival state" in the ischemic hemisphere and angiogenesis in the contralesional side, respectively. These vascular changes in both hemispheres after effective treatment are likely to contribute to enhanced recovery after stroke.

Original languageEnglish (US)
Article numbere24551
JournalPloS one
Volume6
Issue number9
DOIs
StatePublished - Sep 1 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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