The Role And Mechanism Of MiR-29a In Chronic Heart Failure Malignant Arrhythmia

Chronic heart failure is the end stage of all sorts of cardiac diseases,and mortality remains high.The main cause of death are heart failure and malignant arrhythmia.The malignant arrhythmia caused by I_NaLaL increase is the important molecular mechanisms for the death of patients with chronic heart failure.Plenty of studies point to microRNA play key roles in cardiac diseases,they play a negative regulation role in INaL related genes,and increase INaL,serious consequences for patients.The article researchs the role of miRNA in INaL in chronic heart failure.Objective:The application of qRT-PCR and Western blot to explore the relationship between miR-29a and Late Sodium Current related gene SCN5A in chronic heart failure canines'myocardium and chronic heart failure patients'plasma.Then,explore the molecular mechanism of chronic heart failure and malignant arrhythmia.Method:1.Build canines'model of chronic heart failure.The implanted pacer in canines was set as the ventricular asynchronous pacing mode and programmed at260±10 bpm/min for four weeks.2.Screen out some express differences miRNA between healthy canines and chronic heart failure model of canines'myocardium with gene chip.Then,verify the gene chip's results with qRT-PCR,screen out the miRNA that have significant difference.And verify the miRNA whether differences in healthy person and chronic heart failure person.From the above,we found the gene miR-29a.3.Use the target gene prediction software?Targetscan,miRanda,miRbase?,We forecast the target gene of miR-29a is SCN5A,the encoding protein is Nav1.5.And confirm that with dual-luciferase reporter system.4.miR-29a mimics were transfected with myocardial cells?DCYC?.Verify whether the overexpression of mi R-29a could down-regulate the expression of target protein Nav1.5 with WB,and cause the abnormal increase of late sodium current.Result:We screen out a miRNA with gene chip and qRT-PCR,miR-29a in chronic heart failure canines and chronic heart failure patients are unusually elevated.And confirm the target gene of miR-29a is SCN5A with dual-luciferase reporter system.miR-29a mimics were transfected with myocardial cells,the overexpression of miR-29a could down-regulate the expression of target protein Nav1.5.Conclusion:miR-29a can down regulate the transcription and expression of target gene SCN5A,and cause the abnormal increase of late sodium current,and cause malignant arrhythmia.