Pharmacogenomics of cardiovascular pharmacology: pharmacogenomic network of cardiovascular disease models.
The most important strategies in pharmacogenomics are gene expression profiling and the network analysis of human disease models. We have previously discovered novel drug target candidates in cardiovascular diseases through investigations of these pharmacogenomics. The significant induction of S100C mRNA and protein expression was detected in the rat pulmonary hypertension and myocardial infarction model. We also found increased taurine in hypoxia, a calcium-associated cytoprotective compound, to suppress the hypoxia-induced S100C gene expression and vascular remodeling. These results suggest that S100C may be one of the potential novel drug targets in hypoxic or ischemic diseases. Delayed cerebral vasospasm after aneurysmal subarachnoid hemorrhage causes cerebral ischemia and infarction. Using a DNA microarray, a prominant upregulation of heme oxygenase-1 (HO-1) and heat shock protein (HSP) 72 mRNAs were observed in the basilar artery of a murine vasospasm model. Antisense HO-1 and HSP 72 oligodeoxynucleotide inhibited HO-1 and HSP 72 induction, respectively, and significantly aggravated cerebral vasospasm. Moreover, we have also developed a unique heart failure model in zebrafish and identified several candidate genes as novel drug targets. These results suggest that pharmacogenomic network analysis has the potential to bridge the gap between in vitro and in vivo studies and could define strategies for identifying novel drug targets in various cardiovascular diseases.
Tanaka
Toshio
T
Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Japan. tanaka@doc.medic.mie-u.ac.jp
Oka
Takehiko
T
Shimada
Yasuhito
Y
Umemoto
Noriko
N
Kuroyanagi
Junya
J
Sakamoto
Chikara
C
Zang
Liqing
L
Wang
Zhipeng
Z
Nishimura
Yuhei
Y
D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000187:drug effects*; D015316:Genetic Therapy; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics; D006333:Heart Failure / Q000235:genetics / Q000628:therapy; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics / Q000628:therapy; D010597:Pharmacogenetics; D051381:Rats; D009418:S100 Proteins / Q000235:genetics; D020301:Vasospasm, Intracranial / Q000235:genetics / Q000628:therapy; D015027:Zebrafish / Q000235:genetics
D002317:Cardiovascular Agents; D050884:HSP72 Heat-Shock Proteins; D009418:S100 Proteins; D051547:Heme Oxygenase-1