Translation of ischemic preconditioning to the patient: Prolyl hydroxylase inhibition and hypoxia inducible factor-1 as novel targets for stroke therapy Review uri icon

Overview

MeSH Major

  • DNA-Binding Proteins
  • Ischemic Preconditioning
  • Neuroprotective Agents
  • Nuclear Proteins
  • Procollagen-Proline Dioxygenase
  • Stroke
  • Transcription Factors

abstract

  • Effective therapies for stroke must interdict multiple parallel and sequential pathophysiological events. A paradigm which offers insight into multivalent but thoughtfully coordinated protective programs is ischemic preconditioning. A central hypothesis of our group and others is that pharmacological agents that activate programs of gene expression normally induced by ischemic preconditioning will be effective agents for the prevention and treatment of stroke. Inhibitors of a class of enzymes, the hypoxia inducible factor-1 (HIF-1) prolyl hydroxylases stabilize the transcriptional activator HIF-1 and activate target genes involved in compensation for ischemia, including erythropoeitin (Epo) and vascular endothelial growth factor (VEGF). Here, we review evidence suggesting that the HIF-1 prolyl hyroxylases are inhibited during ischemic preconditioning and that pharmacological inhibitors of these enzymes are viable targets for stroke therapy.

publication date

  • November 2004

Research

keywords

  • Review

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1161/01.STR.0000143216.85349.9e

PubMed ID

  • 15472113

Additional Document Info

start page

  • 2687

end page

  • 9

volume

  • 35

number

  • 11 SUPPL. 1