Protein changes observed in pacing‐induced heart failure using two‐dimensional electrophoresis

Abstract

Rapid ventricular pacing in dogs results in a low output cardiomyopathic state which is similar to idiopathic dilated cardiomyopathy in man. However, the pathophysiological mechanisms which cause this failure following pacing are unknown. Five dogs underwent rapid ventricular pacing. Hearts were stimulated at 245 beats per min (bpm) for four weeks and then reduced to 190 bpm to stabilize the failure. Six unoperated dogs were used as controls. This paper compares the two-dimensional gel electrophoresis (2-DE) protein patterns of left ventricular samples from the paced myocardium with the control dogs. Changes in protein expression were analyzed qualitatively and semi-quantitatively. In the paced dog samples 69 protein spots were significantly altered of which 42 were decreased and 27 were elevated. One qualitative change was observed: elongation factor Tu was present only the control hearts. Of these proteins, 20 have been identified by a combination of N-terminal protein microsequencing, peptide mass profiling by mass spectrometry, amino acid compositional analysis, and by comparison with databases of canine and human ventricular proteins. Ten of these are associated with mitochondria and energy production, including: pyruvate dehydrogenase E1 component, isocitrate dehydrogenase subunit alpha, HSP60 and HSP70, creatine kinase M and fatty acid binding protein. The cytoskeletal protein desmin was detected in reduced quantities and a spot corresponding to a fragment of desmin was increased. These results indicate that the development of heart failure in the paced dog involves alterations in mitochondrial energy production, the cytoskeleton and calcium activation.

Two-dimensional gel electrophoresis of Mytilus galloprovincialis differences in protein expression between intertidal and cultured mussels

“…2). An identical approach has also been applied to other species (Higginbotham et al 1991, Heinke et al 1998, Tsuji et al 1999, Vasseur et al 1999) and similar results were obtained.…”

Dynamic expression of proteins associated with adventitial remodeling in adventitial fibroblasts from spontaneously hypertensive rats

“…The phosphorylation of EF-Tu is increased in response to ischemia and in mitochondria from ischemic hearts [25] . Otherwise, EF-Tu content nearly disappears in pacing-induced heart failure, along with a number of other mitochondrial proteins [27] . The status of EF-Tu in hypertension or abnormal vasculature remains elusive.…”

A better understanding of molecular mechanisms underlying human disease

“…They studied the pacing-induced dilated-type heart failure in dogs by 2-DE, finding alterations in the same classes of proteins as those in human DCM (cytoskeletal and myofibrilar proteins, proteins associated with stress responses and proteins associated with mitochondria and energy production) [239,240]. Bovine heredity DCM, a good potential model of human DCM, was analysed by the same group using 2-DE as well [241].…”