Title : Exploring new biomarkers of cardiomyopathy
Abstract:
Myocardial hypertrophy manifests magnification of cardiomyocyte volume rather than number increasing in the adult heart. The differentiation of cardiomyocytes shortly terminates after birth. The cardiomyocytes no longer proliferate like other tissue cells. Myocardial hypertrophy is an important risk factor underlying cardiovascular diseases. No matter how myocardial hypertrophy does, which eventually leads to myocardial dysfunction and heart failure. In despite of that myocardial hypertrophy has been studied over years, its molecular mechanism remains to be addressed. Hypertrophic growth of cardiac myocytes requires a large amount of protein synthesis to meet its needs of this growth.
RNA Pol III genes (RNA Polymerase III-dependent genes) include tRNAs and 5S rRNAs, which participated in protein synthesis and are dominant factors in protein production. Brf1 (TFIIB-related factor 1) is a key regulator of RNA Pol III gene transcription. In the past dozens of years, we have been studying the roles of deregulation of Brf1 and its target genes, RNA Pol III genes in human diseases. We have found that Brf1 expression and RNA Pol III gene transcription are dramatically increased in cell proliferation, cell transformation, and tumor development. To explore whether Brf1 and RNA Pol III genes involve myocardial hypertrophy, we have detected the changes of Brf1 and RNA Pol III genes. These results indicate that Brf1 is overexpressed in human samples of myocardial hypertrophy. Our studies have demonstrated that deleted Brf1 (Brf1-/-) in mouse causes change in myocardial structure. Electronic microscope analysis of the heart tissues of Brf1-/- mouse reveals the gap of Intracellular myocardium space is enlarged. Ultrastructure analysis results appear in changes in metabolism in Brf1-/- mouse. The particles of liver glycogen in heart tissue are dramatically decreased, but the lipid droplets are enhanced. By using ISO-induced rat myocardial cell line H9C2 to construct a cell model of myocardial hypertrophy, the results show that the cardiac hypertrophy markers in the cells, ANP, BNP, and the myocardial fibrosis marker Collage-1 is highly expressed. Interestingly, high expression of these biomarkers of cardiac hypertrophy accompanied with high level of Brf1 in the cells. RNA Pol III gene transcription is also increased. These studies demonstrate that Brf1 indeed plays a critical role in myocardial hypertrophy. Brf1 and RNA Pol III genes may be the new biomarkers of myocardial hypertrophy, which will be developed as novel target of cardiomyopathy.
Audience Take Away Notes:
- Brf1 expression and transcription of RNA Pol III genes are increased in the cells of myocardial hypertrophy.
- Brf1 is overexpressed in human heart tissues of myocardial hypertrophy.
- Deleted Brf1 gene causes ultrastructure alteration of heart tissue of Brf1 -/- mouse.
