The Wilms' tumor suppressor Wt1 is expressed in the coronary vasculature after myocardial infarction.
Expression of the Wilms' tumor gene Wt1 in the epicardium is critical for normal heart development. Mouse embryos with inactivated Wt1 gene have extremely thin ventricles, which can result in heart failure and death. Here, we demonstrate that Wt1 can be activated in adult hearts by local ischemia. Wt1 mRNA was increased more than twofold in the left ventricular myocardium of rats between 1 day and 9 wk after infarction. Wt1 expression was localized by means of mRNA in situ hybridization and immunohistochemistry to vascular endothelial and vascular smooth muscle cells in the border zone of the infarcted tissue. A strikingly similar distribution was seen for vascular endothelial growth factor and two different cell proliferation markers in the coronary vessels of the ischemic heart. No Wt1 could be detected in the vasculature of the noninfarcted right ventricles. Wt1 expression in the coronary vessels of the ischemic heart was mimicked by exposure of rats to normobaric hypoxia (8% O2) and 0.1% CO, respectively. These findings demonstrate that Wt1 is expressed in the vasculature of the heart in response to local ischemia and hypoxia. They suggest that Wt1 has a role in the growth of coronary vessels after myocardial infarction.
Wagner
Kay-Dietrich
KD
Johannes-Müller-Institut für Physiologie and, Klinik für Innere Medizin I, Humboldt-Universität, Charité, 10117 Berlin, Germany.
Wagner
Nicole
N
Bondke
Anja
A
Nafz
Benno
B
Flemming
Bert
B
Theres
Heinz
H
Scholz
Holger
H
D000818:Animals; D002455:Cell Division; D015687:Cell Hypoxia; D003331:Coronary Vessels / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000032:analysis; D004730:Endothelium, Vascular / Q000378:metabolism; D017379:Hypertrophy, Left Ventricular / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008222:Lymphokines / Q000032:analysis; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D015533:Transcriptional Activation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D025721:WT1 Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D025721:WT1 Proteins