Abstract
BackgroundThe present study aimed at using a proteomics based approach to: a) analyze and contrast the proteome of the healthy and isoproterenol induced hypertrophied hearts and b) identify potential biomarkers for diagnosis of cardiac hypertrophy.MethodsMale Sprague Dawley (SD) rats were administered isoproterenol (ISO, 5 mg/kg, sc, once daily) for 14 days to induce cardiac hypertrophy. There was a significant (p<0.05) increase (~ 55%) in the heart weight to tail length ratio after 14 days of treatment and cardiac hypertrophy was evidenced by significant increase of β-MHC and ANP, two indicative markers of cardiac hypertrophy, in the treated heart compared to that of control. Following confirmation of hypertrophy, 2DE of the tissue samples was done followed by MS/MS analysis of the protein spots to obtain a proteomic view for identification of novel biomarkers.ResultsSeveral important proteins were identified by proteomics analysis. They belong to the major functional categories such as cholesterol and protein metabolism, muscle contraction and development, transport, TCAcycle, ATP-biosynthesis, chaperone, signal transduction, DNA synthesis and ubiquitinisation. Careful examination of these protein spots by image analysis led to the successful identification of 7 differentially expressed proteins in the diseased sample. Further extension of this work for validation of differential expression of these proteins was also achieved by RTPCR and western blotting.ConclusionsOur results demonstrate characteristic protein expression profile in control and hypertrophy condition in SD rats and also expand the existing knowledge on differentially expressed proteins in hypertrophy. The study signifies the importance of reduced expression of a novel protein such as Prohibitin (PHB) which may be associated with the cardiomyocytes growth and cardiac hypertrophy. However, further work is necessary to confirm the role of PHB in human heart and its potential role in diagnostic and therapeutic intervention in the clinic.
Highlights
The present study aimed at using a proteomics based approach to: a) analyze and contrast the proteome of the healthy and isoproterenol induced hypertrophied hearts and b) identify potential biomarkers for diagnosis of cardiac hypertrophy
The mRNA levels of hypertrophic marker, β-MHC and ANP were analyzed by Real time PCR which showed elevated levels of this mRNA in Hyp heart compared to Con heart (Figure 1C & D)
We demonstrate that isoproterenol induced cardiac hypertrophy effects at the molecular level, affecting the cardiac protein expression profiles in Sprague Dawley (SD) rats
Summary
The present study aimed at using a proteomics based approach to: a) analyze and contrast the proteome of the healthy and isoproterenol induced hypertrophied hearts and b) identify potential biomarkers for diagnosis of cardiac hypertrophy. Cardiac hypertrophy is characterized by a chronic physiological increase in cardiac muscle mass resulting from systolic or diastolic wall stress. Isoproterenol, a catecholamine, induced cardiac hypertrophy represents the most widely used model which mimics the sustained adrenergic stimulation and represents an important hallmark of the pathogenesis of maladaptive cardiac hypertrophy [5]. Cardiac hypertrophy was followed by progressive heart failure with functional deficits similar to human heart failure [7]
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