Temporal and spatial expression of hypoxia-inducible factor-1alpha and vascular endothelial growth factor in a rat model of myocardial ischemia with or without reperfusion.
OBJECTIVE
Although hypoxia-inducible factor-1alpha (HIF-1alpha) plays a major role in the prevention of myocardial ischemia, the temporal and spatial patterns of expression of HIF-1alpha in myocardial ischemia-reperfusion are not well known. This study examined the role of HIF-1alpha and vascular endothelial growth factor (VEGF) in myocardial ischemia-reperfusion.


METHODS
Adult Wistar rats were studied after ligation of the left anterior descending coronary artery (LAD) for 30 min and then after reperfusion. HIF-1alpha and VEGF were measured immediately after relief of occlusion and at 30 min, 1, 3, 6, and 24 h after reperfusion. HIF-1alpha and VEGF proteins were also measured 6 h after permanent occlusion of the LAD.


RESULTS
HIF-1alpha and VEGF mRNA increased 1.8- and 1.4-fold, respectively, immediately after relief of occlusion and reached a maximum of 4.3- and 2.3-fold, respectively, at 3 h after reperfusion and remained elevated up to 24 h. HIF-1alpha and VEGF proteins increased immediately after relief of ischemia. HIF-1alpha protein significantly increased from 0.5 h to 24 h after reperfusion and VEGF protein significantly increased from 1 h to 6 h after reperfusion compared to the sham control. Administration of HIF-1alpha antisense oligonucleotide before ligation of the LAD significantly inhibited VEGF protein expression induced by ischemia-reperfusion. Immunohistochemical study showed increased immunoreactivity of HIF-1alpha and VEGF in the jeopardized myocardium after ischemia-reperfusion. HIF-1alpha and VEGF proteins were increased at 6 h after permanent occlusion of the LAD.


CONCLUSIONS
This study demonstrated that HIF-1alpha and VEGF were co-induced in a temporal and spatial pattern after ischemia-reperfusion in the rat ventricular myocardium.
Lu
Ming-Jen
MJ
Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Chang
Hang
H
Chang
Chih-Chuan
CC
Wang
Bao-Wei
BW
Shyu
Kou-Gi
KG
D000818:Animals; D004195:Disease Models, Animal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A