| Heart Failure is the final stage of various heart disease, and myocardial infarction (MI) is an most important factor lead to heart failure (HF). Thus, prevention and treatment of chronic heart failure (CHF) after MI is still an important health issue both local and the world. Sudden cardiac death caused by malignant arrhythmia is one of the leading causes of death in CHF patients. Improving the electrical activity of cardiac myocytes and reducing the incidence of malignant arrhythmia is an crucial measure to improve the prognosis, to prolong life expectancy and to enhance life quality of patients with CHF.This research aimed to study the mechanism of the splicing factor RBM25 and LUC7L3 on the pre mRNA of SCN5A, and the effect of those abnormal alternative splicings on the cardiac sodium channel function. We aimed to observe whether gene intervention can be an effective therapy to reduce Navl.5 associated malignant arrhythmia by myocardial injection of lentivirus carrying RBM25/LUC7L3 siRNA. This research also object to observe the relationship between the activation of RAAS and the expression of RBM25, to explore whether the increase of RBM25 splicing factor is another mechanism of RAAS on the expression of Nav1.5, and to study whether restraining of RAAS by captopril and valsartan can reduce the abnormal alternative splicing of Nav1.5.The main findings of our research are as follows:1) the expression of RBM25/ LUC7L3 negatively correlated with the expression of full-length Nav1.5 on both the cell and animal level; 2) RBM25 siRNA lentivirus intervention helpful to improve the recovery rate of ventricular arrhythmia and reduce the mortality rate; 3) RAAS activation result in higher expression of RBM25 and lower Navl.5 expression; 4) RAAS intervention reduce the incidence and improve the recovery rate of ventricular arrhythmia; 5) find a alternative splice directly associated with RBM25, and this alternative splice have difference between groups. |
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