Research Of MiR-21 And Its Target Genes Regulating Hcy Induced Myocardial Remodeling

Objective: Rats were fed with 3% methionine to establish a model of heart failure.To explore the role of mi R-21/PTEN and mi R-21/PDCD4 signaling pathway in this process,provide new exploration ideas for the diagnosis and treatment of heart failure.Methods: Thirty Wistar rats were randomly divided into experimental group(3% Met)(n=15)and control group(n=15).3% Met group was given 3% methionine feed,and control group was fed with normal diet.The two groups were given feed as needed,water was changed daily,and the body weight of the rats was recorded weekly.Both groups were kept in the same environment.After 12 weeks,the rats underwent echocardiography,measuring IVS,LVDD,LVSD,and calculation of left ventricular EF% and FS%.Heart rate and blood pressure were monitored by Hemodynamic.The levels of homocysteine(HCY)and NT-pro BNP in plasma were monitored by the method of ELISA,and the myocardial tissue of the rats was taken for pathological examination such as HE,Masson and Tunel.RT-PCR method was used for determination of micro RNA-21(micro RNA-21,mi RNA-21),PTEN,m RNA expression level of PDCD4,Western blot analysis expression levels of PDCD4,PTEN protein in myocardial tissue.Results: In the 3% Met group,the skin appeared dull and thin,yellowed gradually,with varying degrees of hair loss,slow weight gain,and even negative growth.After 5 weeks of experimentation,the body weight and body weight growth rate of the 3% Met group were significantly lower than control group.After 12 weeks,the body weight and cardiac weight index(HWI)of the 3% Met group were lower than control group.The results were statistically significant.The results of echocardiography showed that EF%,FS%,IVS decreased,LVDD and LVSD increased in the 3% Met group,and the difference was statistically significant.Hemodynamic parameters showed that arterial blood pressure decreased in the 3% Met group,while there was no significant difference in left internal pressure and HR.The ELISA results showed that the plasma levels of HCY and NT-pro BNP in the 3% Met group were significantly higher than those in the control group.The difference was statistically significant.HE staining showed that the myocardial arrangement was disordered and the myocardial space was enlarged in the 3% Met group.Masson staining showed an increase in fibrosis in the 3% Met group,and the collagen volume fraction was higher than the control,which was statistically significant.Tunel results showed that apoptotic cells were found in both groups.The apoptotic cells in the 3% Met group increased,and the apoptotic index(AI%)in the 3% Met group was higher than that in the control group,which was statistically significant.Western blot results showed that the expression levels of PTEN and PDCD4 in myocardial tissue of 3% Met group were significantly higher than those in the control group.The results of RT-PCR showed that the m RNA expression level of mi RNA-21 was increased in the 3% Met group.The m RNA expression of PTEN and PDCD4 was consistent with the expression of the protein,and was up-regulated in the 3% Met group.Conclusions: Hyperhomocysteinemia induced by oral methionine in rats can lead to heart failure in rats.mi RNA-21/PTEN and mi RNA-21/PDCD4 signaling pathways are involved in the regulation of Hcy-induced heart failure.