Proteomic Analysis Reveals Significant Alternations of Cardiac Small Heat Shock Protein Expression in Congestive Heart Failure.

Abstract: Background: Because congestive heart failure (CHF) is a complex syndrome with many different underlying mechanisms of worsening of heart function, it is important to recognize the global alternations in protein expression associated with the processes of CHF. Methods and Results: The purpose of our study was to use a proteomic approach to investigate global alternations in protein expression in tachycardia induced CHF dogs. We compared the 2-dimensional electrophoresis protein patterns of left ventricular samples from the normal with those from failing myocardium. Differentially expressed cardiac proteins showed approximately 500 cardiac protein spots. A total of 20 spots (14 increased, 6 decreased) was altered in CHF, whereas the more distinguishably increased spots in CHF were identified by using mass spectrometry as alpha B crystallin, heat shock protein (HSP) 27, and HSP20, which maintain both the morphologic and functional integrity of the cardiomyocytes and increase tolerance against various types of stress. Because phosphorylation is one of the most important posttranslational modifications, we evaluated whether or not the overexpressed small HSPs were phosphorylated in CHF. Phosphoprotein staining and Western blotting demonstrated that the phosphorylation of alpha B crystallin at serine (Ser)-59 site and of HSP27 at both Ser-78 and Ser-82 sites increased in CHF. Conclusion: Proteomics studies can provide new insights into molecular mechanisms in CHF and phosphorylated small HSPs may be involved in preventing cardiac dysfunction. [Copyright &y& Elsevier]