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Open Access Research article

Genome response to tissue plasminogen activator in experimental ischemic stroke

Glen C Jickling1*, Xinhua Zhan1, Bradley P Ander1, Renée J Turner1, Boryana Stamova1, Huichun Xu1, Yingfang Tian1, Dazhi Liu1, Ryan R Davis1, Paul A Lapchak2 and Frank R Sharp1

Author Affiliations

1 Department of Neurology and M.I.N.D. Institute, University of California at Davis, Sacramento, California 95817, USA

2 Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA

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BMC Genomics 2010, 11:254  doi:10.1186/1471-2164-11-254

Published: 21 April 2010

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 ≤ 0.05, fold change ≥ |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.