Altered hepatic gene expression profiles associated with myocardial ischemia.
BACKGROUND
Acute coronary syndrome is sometimes accompanied by accelerated coagulability, lipid metabolism, and inflammatory responses, which are not attributable to the cardiac events alone. We hypothesized that the liver plays a pivotal role in the pathophysiology of acute coronary syndrome. We simultaneously analyzed the gene expression profiles of the liver and heart during acute myocardial ischemia in mice.


RESULTS
-Mice were divided into 3 treatment groups: sham operation, ischemia/reperfusion, and myocardial infarction. Mice with liver ischemia/reperfusion were included as additional controls. Marked changes in hepatic gene expression were observed after 24 hours, despite the lack of histological changes in the liver. Genes related to tissue remodeling, adhesion molecules, and morphogenesis were significantly upregulated in the livers of mice with myocardial ischemia/reperfusion or infarction but not in those with liver ischemia/reperfusion. Myocardial ischemia, but not changes in the hemodynamic state, was postulated to significantly alter hepatic gene expression. Moreover, detailed analysis of the signaling pathway suggested the presence of humoral factors that intervened between the heart and liver. To address these points, we used isolated primary hepatocytes and showed that osteopontin released from the heart actually altered the signaling pathways of primary hepatocytes to those observed in the livers of mice under myocardial ischemia. Moreover, osteopontin stimulated primary hepatocytes to secrete vascular endothelial growth factor-A, which is important for tissue remodeling.


CONCLUSIONS
Hepatic gene expression is potentially regulated by cardiac humoral factors under myocardial ischemia. These results provide new insights into the pathophysiology of acute coronary syndrome.
Ootsuji
Hiroshi
H
Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
Honda
Masao
M
Kaneko
Shuichi
S
Usui
Soichiro
S
Okajima
Masaki
M
Okada
Hikari
H
Sakai
Yoshio
Y
Takamura
Toshinari
T
Horimoto
Katsuhisa
K
Takamura
Masayuki
M
D000818:Animals; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009203:Myocardial Infarction / Q000235:genetics; D017202:Myocardial Ischemia / Q000235:genetics* / Q000378:metabolism; D015425:Myocardial Reperfusion; D053495:Osteopontin / Q000097:blood / Q000235:genetics; D015398:Signal Transduction; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A; D053495:Osteopontin