The Role Of Wnt3a/?-catenin Signal Pathway In Cardiomyocyte Apoptosis Resist In Heart Failure Induced By Survivin

Background: Heart failure is the terminal stage of various cardiovascular diseases, with a high mortality rate, high cost and high morbidity, and brings huge burden to individuals and society. Ventricular remodeling is an important pathological changes of heart failure,and myocardial apoptosis is one of the key mechanisms for ventricular remodeling.Researches revealed that Wnt/?-catenin,which as classical Wnt signaling pathway,participate in cardiomyocyte hypertrophy and apoptosis process.Wnt3a,one of wnt family,works complex in cardiomyocyte. Survivin is a member of the inhibitor of apoptosis family,some researchs found it anti-apoptosis in cardiomyocyte with heart failure, while upstream signal of survivin remainning unclear.Aims:1?To investigate the expressions of Wnt3a,?-catenin,survivin in cardiomyocyte of heart failure rat model ;2?To investigate the expressions and relations of Wnt3a,?-catenin,survivin in primary cardiomyocytes and heart failure myocytes induced by DOX ;3?To investigate the functions and mechanisms of overexpress wnt3a,survivin and interference wnt3a during heart failure myocytes apoptosis.Methods:1?Twenty-one male Sprague-Dawley rats divided into three groups randomly.Thoracic aorta constriction were applied to the operation group,the sham-operation group underwent the same process except artery constriction,the blank group were given no intervention.All animals took echocardiogram test regularly.HE staining,Immunohistochemical staining,western blot experiments were applied to the cardiac muscular tissue.2?Established overexpress wnt3a,overexpress survivin and interference wnt3a adenovirus vectors,Cultured primary caridiomyocytes and used DOX to induce heart failure,then transfected with adenovirus.Western blot experiments was applied to investigate the protein expressions.TUNEL was applied to investigate the functions of overexpress wnt3a?overexpress survivin and interference wnt3a during heart failure myocytes apoptosis.Results:1?After 18 weeks operation group rats resulted in heart failure.HE staining of operation group revealed myocyte hypertrophy, arrangement disorderly, uneven nuclei size. Immunohistochemistry and western blot results revealed the expression of wnt3a,?-catenin, survivin and caspase-3 in operation group were higher than in the other two groups, especially survivin and caspase-3 were far higher. Bcl-2 expressed lower in operation group ;2?Analysis of western blot result after transfection,both overexpress and interference wnt3a were unable to performance impact on survivin in primary myocytes or heart failure myocytes induced by DOX. Overexpress survivin promoted ?-catenin expression in primary myocytes, but not in heart failure myocytes. Overexpress Wnt3a and survivin could promote the expression of Bcl-2 in primary myocytes, overexpress survivin could also weaken DOX inhibition of Bcl-2 in heart failure myocytes, while overexpress Wnt3a lacked a similar function. Overexpress Wnt3a and survivin inhibited caspase-3 expression in primary myocytes and weakened the caspase-3 promotion come from DOX in heart failure myocytes, while interference Wnt3a resulted in opposite ;3?Both overexpress Wnt3a and survivin showed anti-apoptosis in heart failure myocytes induced by DOX, while interference Wnt3a resulted in opposite.Conclusion:1?The high expression of wnt3a, ?-catenin and survivin in heart failure rats may reflect the body negative feedback mechanism of self-protection ;2.Both wnt3a and survivin could reduce cells apoptosis induced by DOX, probably related to downregulation of caspase-3, further more the anti-apoptosis function of survivin may also related to upregulartion of Bcl-2 ;3.The functions of survivin in heart failure myocytes maybe extend outside of cell membrane and attribute to direct myocyte transfection and paracrine.