Abstract P219: Differences in Phosphoproteins in Rodent versus Human Hearts: Implications for Translational Studies of Hypertensive Heart Disease

Abstract

Background: Rodent models are commonly used to study hypertensive heart disease. Several recent studies have probed the level of correlation between specific signaling pathways and proteins in human and rodents. Current evidence is overwhelming that protein phosphorylations play a key role in cardiac remodeling. Methods: Left ventricular tissue samples were obtained from human systolic failing (n=5) and control (n=5) hearts and 3 rat models of hypertensive heart failure (aortic banding, Dahl salt-sensitive, and spontaneously hypertensive rats (SHR)) and corresponding controls. Total proteins were extracted and and phosphoenrichment performed. Phosphoproteins were separated by 2D-DIGE with Cydye staining. Gel images were registered and rectified for composite analysis and statistical comparisons using pixel intensity. Phosphoproteins were identified by MALDI-TOF/TOF Mass Spectrometry. Results: The patterns of overall protein abundance from normal and failing hearts were not statistically different. However, when the composite of human hearts were compared with composite patterns of phosphoproteins in normal and failing rodent hearts, there were profound differences in the phosphoprotein patterns in 26% of pixels in registered images (P < 0.05). Targeted pair wise analyses showed differences (P < 0.05) between human and rodent hearts for troponin T, myosin light chain, peroxiredoxin, and haptoglobin phosphorylations. Conclusions: Together, the present results indicate significant differences in cardiac phosphoproteins in human versus rodent heart and the importance of confirming findings from rodent studies in humans for translational studies of kinases, phosphatases, and phosphoproteins. This may specifically relate to studies of phosphorylation of myosin light chain and troponin.