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

• Published in: Journal of the Formosan Medical Association Vol. 104; no. 10; pp. 707 - 714
• Main Authors: Lu, Ming-Jen, Chang, Hang, Chang, Chih-Chuan, Wang, Bao-Wei, Shyu, Kou-Gi
• Format: Journal Article
• Language: English
• Published: Singapore 臺灣醫學會 01.10.2005
• Subjects: Animals; Disease Models, Animal; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Myocardial Ischemia - metabolism; Myocardial Reperfusion; Myocardial Reperfusion Injury - metabolism; Rats; Rats, Wistar; Vascular Endothelial Growth Factor A - metabolism; Hypoxia-inducible factor 1, alpha subunit; Vascular Endothelial Growth Factor A; Myocardial ischemia; Reperfusion
• ISSN: 0929-6646
• DOI: 10.29828/JFMA.200510.0002

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. 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. 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. 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.