Study On Protein Modification And Signal Pathway Regulation Of Remodeling Myocardium In Hypertrophic And Dilated Cardiomyopathies

Background: Hypertrophic cardiomyopathy (HCM) Is characterised by cardiomyocyte hypertrophy, disarray and interstitial fibrosis with left ventricular hypertrophy being predominant, which normally involves the inter-ventricular septum. Familial hypertrophic cardiomyopathy (FHC) is a genetically heterogeneous autosomal dominant inherited heart disease and has been linked to at least 25 mutations in cardiac troponin I (cTnI). In 2003, we were the first to report that a novel mutation, cTnI Arginine145→tryptophan (cTnI R146W in the mouse sequence) was linked with hypertrophic cardiomyopathy among Chinese people. Recombinant adenoviruses containing enhanced green fluorescence protein (EGFP) and cTnI R146W ( Adc cTnI R146W-EGFP) were constructed and successfully transferred into myocardium of mice. The cTnI R146W-EGFP mutant mice were demonstrated typical ventricular hypertrophy. Heart failure occupies the predominant position of morbidity and mortality in cardiovascular disease and represents the end-stage in development of many cardiovascular diseases. In 2003, a Japanese researcher Okazaki and his fellow intraperitoneally injected monoclonal anti-cTnI antibodies into BALB/c wild-type mice. Comperased with normal mice, these mice showed enlarged end-systolic and end-diastolic volume of the left ventricle 3-fold and 1.3-fold, respectively, and decreased the contractile function by 60% in 12 weeks. Some of the anti-cTnl antibody injected mice develop more severe disease within 40 weeks. The ejection fraction of such mice is lower than 15%. They concluded that antibodies against cTnI are considered to be responsible for the DCM in BALB/c wild-type mice. Dilated cardiomyopathy is the most common disorder that results in heart failure, while the remodeling process in myocardial failure involves changes in ventricular structure and performance. It is now appreciated that it is also associated with changes in thin filament composition and function. Recent studies indicate that the protein properties of thin filament play an important...