Genome response to tissue plasminogen activator in experimental ischemic stroke

BMC Genomics. 2010 Apr 21:11:254. doi: 10.1186/1471-2164-11-254.

Abstract

Background: Tissue plasminogen activator (tPA) is known to have functions beyond fibrinolysis in acute ischemic stroke, such as blood brain barrier disruption. To further delineate tPA functions in the blood, we examined the gene expression profiles induced by tPA in a rat model of ischemic stroke.

Results: tPA differentially expressed 929 genes in the blood of rats (p <or= 0.05, fold change >or= |1.2|). Genes identified had functions related to modulation of immune cells. tPA gene expression was found to be dependent on the reperfusion status of cerebral vasculature. The majority of genes regulated by tPA were different from genes regulated by ischemic stroke.

Conclusions: tPA modulates gene expression in the blood of rats involving immune cells in a manner that is dependent on the status of vascular reperfusion. These non-fibrinolytic activities of tPA in the blood serve to better understand tPA-related complications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier
  • Brain Ischemia / chemically induced
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / genetics*
  • Gene Expression Profiling*
  • Leukocytes / immunology
  • Leukocytes / metabolism*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion
  • Stroke / drug therapy*
  • Stroke / genetics*
  • Tissue Plasminogen Activator / therapeutic use*

Substances

  • Tissue Plasminogen Activator