Abstract
Our previous study showed that CD151 promotes neovascularization and improves blood perfusion in a rat hindlimb ischemia model. In this study, we investigated whether CD151 promotes neovascularization and improves ventricular function after myocardial infarction in rats and the mechanisms involved. Rats were subjected to sham surgery or coronary artery ligation. We used rAAV for direct delivery of the human CD151 gene into the rat myocardium. At 4 weeks after coronary artery ligation, human CD151 mRNA was detected using RT-PCR. Measurement of capillary density was evaluated using immunostaining for von Willebrand factor, and hemodynamic variables and physiological parameters were monitored. Western blot analysis for CD151, PI3K, phosphor-Akt, total Akt, phosphor-eNOS, and total eNOS was performed. In addition, we also observed the effect of CD151 on the expression of VEGF using Western blot analysis. CD151 gene delivery could increase the expression of CD151 at gene and protein levels. Overexpression of CD151 could increase the number of microvessels in the ischemic myocardium and significantly improved the hemodynamic variables after myocardial infarction. In addition, CD151 could activate the PI3K pathway, including activation of Akt and eNOS, but did not affect the expression of VEGF. This study suggested that CD151 could promote neovascularization and improve ventricular function after myocardial infarction in rats. The mechanism may be that CD151 can activate the PI3K pathway and promote neovascularization via the PI3K pathway, without affecting ischemia-induced VEGF expression.
Highlights
Therapeutic angiogenesis may be beneficial in the treatment of ischemia, as has recently been substantiated by a large amount of experimental data
Human CD151 mRNA was detected in the hearts of the acute myocardial infarction (AMI) + Recombinant adenoassociated virus (rAAV)-CD151 group and the ECV304 cells transfected with rAAV-CD151, but not in the other group that received rAAV-GFP or saline (Figure 1)
The results indicated that rAAV-CD151 administration could promote CD151 protein expression, which confirmed that rAAVmediated gene transfer could drive stable long-term expression of the CD151 gene in vivo
Summary
Therapeutic angiogenesis may be beneficial in the treatment of ischemia, as has recently been substantiated by a large amount of experimental data. Coronary collateral vessels and microvascular angiogenesis, which ameliorate the function of the damaged heart, develop as an adaptive response to myocardial ischemia. Previous studies have shown that CD151-induced formation of cord-like structures on matrigel is an in vitro model of angiogenesis. CD151 antibody inhibition of cord-like structures on matrigel seen in NIH3T3 cells was confirmed using HUVECs, suggesting that CD151 may contribute to angiogenesis [1,2]. Our research has revealed that CD151 promotes neovascularization and angiogenesis, which suggests that CD151 is a potential therapeutic reagent for treating ischemia by inducing angiogenesis [3]. Whether CD151 promotes neovascularization and angiogenesis after myocardial infarction in rats is still unclear, ; the precise molecular mechanisms responsible for the function of CD151 are still poorly defined, and the signaling pathways involved need to be better defined
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