Candesartan induces a prolonged proangiogenic effect and augments endothelium-mediated neuroprotection after oxygen and glucose deprivation: Role of vascular endothelial growth factors A and B

Sahar Soliman, Tauheed Ishrat, Anilkumar R Pillai, Payaningal R. Somanath, Adviye Ergul, Azza B. El-Remessy, Susan C. Fagan

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Angiogenesis is a key component of recovery after stroke. Angiotensin II receptor blocker (ARB) treatment improves neurobehavioral outcome and is associated with enhanced angiogenesis after stroke. The purpose of this study is to investigate the temporal pattern of the ARB proangiogenic effect in the ischemic brain and its association with vascular endothelial growth factors VEGF-A and VEGF-B. Wistar rats were exposed to 90-minute middle cerebral artery occlusion and treated with candesartan (1 mg/kg) at reperfusion. The proangiogenic potential of the cerebrospinal fluid was determined at 8, 24, 48, and 72 hours using an in vitro Matrigel tube formation assay. In addition, the expression of VEGF-A and VEGF-B was measured in brain homogenates using Western blotting at the same time points. A single candesartan dose induced a prolonged proangiogenic effect and a prolonged upregulation of VEGF-A and VEGF-B in vivo. In the ischemic hemisphere, candesartan treatment was associated with stabilization of hypoxia-inducible factor-1α and preservation of angiopoietin-1. The effect of ARB treatment on endothelial cells was studied in vitro. Our results identified brain endothelial cells as one target for the action of ARBs and a source of the upregulated VEGF-A and VEGF-B, which exerted an autocrine angiogenic response, in addition to a paracrine neuroprotective effect. Taken together, this study highlights the potential usefulness of augmenting the endogenous restorative capacity of the brain through the administration of ARBs.

Original languageEnglish (US)
Pages (from-to)444-457
Number of pages14
JournalJournal of Pharmacology and Experimental Therapeutics
Volume349
Issue number3
DOIs
StatePublished - Jun 2014

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ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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