A proteomic view of isoproterenol induced cardiac hypertrophy: Prohibitin identified as a potential biomarker in rats

Background: 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. Methods: Male 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 (similar to 55%) in the heart weight to tail length ratio after 14 days of treatment and cardiac hypertrophy was evidenced by significant increase of beta-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. Results: Several 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. Conclusions: Our 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.