Abstract
To evaluate the effects of HIF-1α overexpression on mitochondrial function in aged mice with myocardial ischemia-reperfusion (I/R). Mice were divided into 1) Blank (Sham) group; 2) Ischemia-reperfusion (I/R) group; 3) I/R+2ME2 group (I/R+HIF-1α blocker 2ME2. Compared with Sham group, in I/R group and I/R+2ME2 group, HR slowed down, LVDP and +dp/dtmax decreased, LVEDP, myocardial infarction area, and ROS generation rate was significantly increased; whereas the mitochondrial respiratory function (State3, RCR) and mitochondrial respiratory enzyme activity (NADH-OX, Cytc-OX and SUC-OX) were significantly reduced. Compared with the I/R group, the respiratory function of myocardial mtochondria (State3, RCR) and respiratory enzyme activity of myocardial (NADH-OX, Cytc-OX and SUC-OX) were significantly reduced in the I/R+2ME2 group; and the levels of p-HIF-1α and p-VEGF in the I/R+2ME2 group were significantly decreased. HIF-1α pathway upregulate the respiratory enzyme activity of myocardial and respiratory function of I/R myocardial mitochondria.
Highlights
As our country’s population’s aging process continues to accelerate, the prevalence of acute myocardial infarction (AMI) in the elderly is getting higher and higher
Compared with the Sham group, the mitochondrial respiratory function of the I/R group and the I/R+2ME2 group significantly decrease at the end of reperfusion (P < 0.05); compared with the I/R group, the state3 and respiratory control rate (RCR) of I/R+2ME2 group reduced significantly (P < 0.05) (Table 3)
The activation of HIF-1α can improve the tolerance of cardiomyocytes to ischemia and hypoxia, reducing the apoptosis of cardiomyocytes (Belaidi et al, 2008)
Summary
As our country’s population’s aging process continues to accelerate, the prevalence of acute myocardial infarction (AMI) in the elderly is getting higher and higher. During AMI, myocardial cells can feel hypoxia signal stimulation, thereby activating the hypoxia signaling pathway, starting the gene expression downstream of the signaling pathway, regulating the adaptability of the cell in the hypoxia microenvironment, and maintaining the stability of the internal environment of the cell. In this process, hypoxic signals stimulate cells to induce and activate the expression of HIF-1. HIF-1α has a molecular switch function in the signaling pathway It activates the expression of HIF-1α in cells under hypoxic-ischemic stress, precisely regulates downstream genes, and maintains basic cell energy metabolism (Tekin et al, 2010; Zhu et al, 2008). This study intends to use the myocardial I/R model of aged mice to evaluate the recombinant adeno-associated virus serotype 9 mediated HIF-1α transfection into aged myocardium on mitochondrial respiratory function and enzyme activity, providing a basis for further research on the protective effect of aged ischemic myocardium
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