Research Of The Effect And Mechanism Of High Mobility Group Box-1 On Cardiac Hypertrophy Through Inflammatory

BackgroundCardiac hypertrophy is related to cardiac ischemia,valve damage and hypertrophic cardiomyopathy and is attributed to internal or external stimuli,which leading to change of cardiac morphology.However,the pathogenesis of cardiac hypertrophy has not been fully elucidated,and there is no effective prevention and treatment measures.High mobility group box 1(HMGB1)is highly conserved in all mammals and is expressed consistently in the nucleus of almost all cell types examined.HMGB1,as a late inflammatory factor,is released passively by necrotic cells,and actively by macrophages/monocytes in response to exogenous and endogenous inflammatory stimuli.Overexpression of HMGB1 was observed in human hypertrophic cardiomyopathy heart tissue,so was in cardiac hypertrophy mice model.Evidence shows that HMGB1 plays an important role in the process of cardiac hypertrophy.We aim to study the effect and mechanism of HMGB1 on cardiac hypertrophy both in vivo and in vitro.Objective1.The study is aimed at screening differently expressed genes related to HCM between the HCM and the health to find out the most significantly stimulated signaling protein by using Ingenuity Pathway Analysis(IPA).2.Verify the expression of HMGB1 of heart tissue in HCM patients.3.Discuss the expression pattern of HMGB1 in transverse aortic constriction(TAC)model of mice.Methods1.After collecting the cardiac muscle tissue of the HCM and the health,we use Illumina sequencing technology to screen the differently expressed gene.After that,the analysis of IPA was done to find out the most significantly stimulated signaling protein.2.Immunohistochemical analysis was used to verify the expression in heart tissue in HCM patient.3.After making TAC models,we analyze the the expression pattern of HMGB1 in mice using RTPCR.Results1.Analysis of IPA in human heart tissue was done to find out the most significantly stimulated signaling protein is HMGB1.2.Immunohistochemical analysis was used to verify the expression of HMGB1 in heart tissue in HCM patient is higher than that of control group.3.The TAC model is successful,and HMGB1 is highly expressed in mRNA level.Conclusion1.This study elucidates the signaling pathways significantly changed in hypertrophic cardiomyopathy patients by using IPA.2.We verify the result by using Immunohistochemical analysis in human heart tissue.We got the same result with RNAseq by real time PCR in TAC models in mice.