| Background:Myocardial infarcion is one of the leading cause of mortality worldwide.The development of MI includes the coronary artery stenosis or spasm,the subsequent blunt of blood supply for heart,and the loss of cardiomyocyte due to necrosis and apoptosis.Once MI happened,myocardium is short of blood supply and consume excess oxygen,the microenvironment of myocardium is under hypoxic and ischemic,.a large number of cardiomyocyte lost.Although blunted coronary artery can be reperfused,the reperfusion injury further damaged to the injured myocardium.Therefore,how to preserve cardiomyocyte after MI is an important issue..The major treatments for MI include percutaneous coronary intervention(PCI),antithrombotic therapy,Coronary Artery Bypass Grafting(CABG)and heart transplantation.However,the effect of these treatment are still not satisfy to some extent,which urged us to looking for novel or supplemental treatment.YY1 is a highly conserved nuclear transcriptional factor.It is also called “all-powerful gene” due to its effect of anti-apoptosis,anti-hypertrophy and pro-angiogenesis.YY1 is well expressed in heart,it play roles in a variety of cardiovascular diseases.Hence,the mechanism underlying the regulatory effect of YY1 in cardiovascular diseases attract much attention nowadays,and is also important for MI therapy research.Recently,it has been reported that YY1 can inhibit apoptosis by stimulating the expression of anti-apoptotic gene Survivin,this effect is dependent on the phosphorylation and activation of Akt.It has also been reported that YY1 can promote angiogenesis by inducing VEGFA m RNA transcription.On the other hand,knocking out of YY1 leads to decreasement in angiogenesis.To sum up,YY1 can possibly activate VEGFA and Survivin,inhibit cardiomyocyte apoptosis and promote angiogenesis after MI,improve the hypoxic and ischemic microenvironment,ameliorate cardiomyocyte death after MI.Therefore,up-regulation of YY1 in cardiomyocyte can be considerated as a potential stratagy for CVD treatment.Purpose:To investigate the effects of YY1 on myocardial infarction and the underlying mechanismsMethods:1.Animal experiment:a.C57BL/6J mice were subjected to LAD after the AAV9 mediated Overexpression of YY1.Ventricular function survival rate,myocardial fibrosis,infarction area,andcardiomyocyte apoptosis were measured.b.Angiogenesis was examined by stanning of CD31.VEGFA and HIF-1 ? were assessed byby ELISA,YY1 and Akt protein expression were detected by Western Blot.2.Cell experiment: NRVMs were cultured in ischemia-hypoxia environment which was induced by culturing in glucose free medium and pre-treatment of Na2S2O4.YY1 recombinant plasmid and Akt specific inhibitor LY294002 were applied to cardiomyocyte,apoptosis of cardiomyocyte was observed.The NRVMs were co-cultured with HUVECs,and endothelial tube formation assay with HUVECs were performed to investigate the angiogenesis.Result:1.YY1 is increased in mice heart after MI;YY1 overexpression improve heart function in mice,increases the survival rate,reduces the infarcted area,and reduces the myocardial fibrosis,.Phosphorylation of Akt,HIF-1a,survivin expression,phosphorylation of Akt is elevated after YY1 overexpression.2.YY1 overexpression in cardiomyocytesincreases the vitality,decreasecell apoptosis,increase angiogenesis,promote phosphorylation of Akt and expression of survivin After treated with PI3 K / Akt signaling pathway blocker LY294002 cell viability is decreased,apoptosis increased,angiogenesis decreased,phosphorylation of Akt andsurvivin expression decreasedConclusion:YY1 may have a protective effect on MI,which possibly relates to the activation of PI3K\Akt signaling pathway. |
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