Differential protein expression profiling of myocardial tissue in a mouse model of hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is a genetic disorder caused by mutations in genes encoding sarcomere proteins. The mechanisms involved in the development of cardiac hypertrophy and heart failure remain poorly understood. Global proteomic profiling was used to study the cardiac proteome of mice predisposed to developing HCM. Hearts from three groups of mice (n=3 hearts per group) were studied: non-transgenic (NTG) and cardiac-specific transgenic models over-expressing either the normal (TnI(WT)) or a mutant cardiac troponin I gene (Gly203Ser; TnI(G203S)). Two-dimensional gel electrophoresis (2-DE) coupled with tandem mass spectrometry was used to identify proteins. Image analysis was performed using Progenesis SameSpots. A total of 34 proteins with at least a twofold change in the TnI(G203S) mouse model were identified. Alterations were detected in components involved in energy production, Ca(2+) handling, and cardiomyocyte structure. Expression level changes in cytoskeletal and contractile proteins were well represented in the study, including the intermediate filament protein desmin, which was further investigated in two additional physiological and pathological settings, i.e., exercise treatment, and severe heart failure in a novel double-mutant TnI-203/MHC-403 model of HCM. This study highlights the potential role of tissue proteomic profiling for mapping proteins, which may be critical in cardiac dysfunction and progression to heart failure in HCM.
Lam
Lien
L
Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, Australia.
Tsoutsman
Tatiana
T
Arthur
Jonathan
J
Semsarian
Christopher
C
D000818:Animals; D015153:Blotting, Western; D002312:Cardiomyopathy, Hypertrophic / Q000378:metabolism*; D002853:Chromatography, Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D019210:Troponin I / Q000235:genetics / Q000378:metabolism
D011506:Proteins; D019210:Troponin I