Pharmacogenomics and therapeutic target validation in cerebral vasospasm.
One of the most important pharmacogenomic technologies is transcriptome analysis. We used this method to study the change of gene expression profiles in animal models of cerebral vasospasm. We found novel drug target candidates in cerebral vasospasm through pharmacogenomics. By using differential display and quantitative reverse transcriptase-polymerase chain reaction, we found that heme oxygenase-1 (HO-1) mRNA was prominently induced in the basilar artery and modestly in brain tissue in a murine vasospasm model. There was a significant correlation between the degree of vasospasm and HO-1 mRNA levels in the basilar arteries exhibiting vasospasm. Antisense HO-1 oligodeoxynucleotides (ODN) inhibited HO-1 induction in the basilar arteries, but not in the whole brain tissue. This phenomenon was not observed in the nontreatment, sense HO-1 ODN and scrambled ODN treatment arteries. We report, for the first time, the protective effects of HO-1 gene induction by endogenous or clinical compounds in cerebral vasospasm after subarachnoid hemorrhage, a finding that should provide a novel therapeutic target for cerebral vasospasm.
Tanaka
T
T
Department of Molecular and Cellular Pharmacology, Mie University School of Medicine, Tsu, Japan. tanaka@doc.medic.mie-u.ac.jp
Nishimura
Y
Y
Tsunoda
H
H
Naka
M
M
D000818:Animals; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D006801:Humans; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D015533:Transcriptional Activation; D020301:Vasospasm, Intracranial / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*
D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1