Title : Study of pathological cardiac hypertrophy regression
Abstract:
Heart disease ranks as the first leading cause of death in west countries. No matter pulmonary heart disease or cardiogenic heart disease, heart disease ultimately lead to pathological cardiac hypertrophy (PCH). PCH is an irreversible, high-risk and common cardiomyopathy, and the incidence rate is increasing year by year. PCH exhibits heterogeneity and multi phenotype characteristics, and its mechanism is complex and unclear now. PCH has characteristics, such as abnormal increase in protein synthesis and epigenetic regulation disorders. Our preliminary studies have shown when drug (ISO) and surgical (TAC) induce myocardial hypertrophy of mice significantly upregulates the expression of transcription factor BRF1 and its target gene (RNA Pol III genes) transcription, which are positively correlated with experimental myocardial hypertrophy. The high expression of BRF1 and upregulation of RNA Pol III gene (tRNA and 5S rRNA) transcription have been validated in clinical cases of myocardial hypertrophy. Our previous studies have demonstrated that the abnormally high expression of BRF1 and RNA Pol III genes are closely related to cell proliferation and rapid growth. While RNA Pol III genes play a decisive role in protein synthesis. Alcohol feeding promotes cardiac hypertrophy of animals. Alcohol induces the activation of mitogen and stress-activated protein kinase1 (MSK1), while MSK1 positively mediates BRF1 expression and RNA Pol III gene transcription. Inhibited MSK1 activity reduces BRF1 expression and RNA Pol III gene transcription. Interestingly, ISO also activates MSK1 in immortalized rat heart cells. On other hand, knock down BRF1 expression recovers alcohol-induced cardiac hypertrophy. It implies that inhibition of MSK1 may regression of PCH to provides a new direction of treatment development for the patients of PCH.
