Changes in myocardial protein expression in pacing-induced canine heart failure

Abstract

Canine rapid ventricular pacing produces a low output cardiomyopathic state which is similar to dilated cardiomyopathy. In this study dogs were paced at 245 beats per minute (bpm) for 3±4 weeks until signs of heart failure were apparent. Unpaced dogs were used as controls. A previous study identified myocardial protein changes in the pH region 4±7 following ventricular pacing by using two-dimensional electrophoresis (2-DE) (Heinke et al., Electrophoresis 1998. Many of these proteins were associated with mitochondria, energy metabolism within the cardiomyocyte, the cytoskeleton and calcium cycling. The present study aimed to examine the proteins migrating in the more basic region of the 2-DE pattern using immobilised pH gradient 3±10 strips to separate myocardial proteins. The expression of 31 proteins was altered in the paced myocardium: 21 were decreased and 10 increased. Following the identification of 23 of these spots by either amino acid compositional analysis or peptide mass fingerprinting or a combination of both, we confirm that many of the proteins whose expression is altered following ventricular pacing are associated with the mitochondria and energy production within the cardiomyocyte, including creatine kinase M, triosephosphate isomerase, phosphoglycerate mutase, cytochrome c oxidase, cytochrome b5, hydroxymethyl glutaryl CoA synthase, myoglobin, and 3,2-trans-enoyl-CoA transferase. Additionally, the cytoskeletal protein actin was increased in the paced hearts. These results strongly support the notion that energy production is impaired and mitochondrial dysfunction is involved in the development of heart failure in the paced dog.

Depressed mitochondrial transcription factors and oxidative capacity in rat failing cardiac and skeletal muscles

“…Despite the diversity in the pathogenesis of heart failure, defects in energy metabolism have been implicated in the disease progression (Ingwall 1993; Dzeja et al 2000; Lehman & Kelly, 2002; Ventura‐Clapier et al 2002). Proteomic analysis has shown that many of the cardiac proteins altered in CHF are involved in energy metabolism (Heinke et al 1999). Marked reductions in the complexes of the respiratory chain have been described in both cardiac and skeletal muscles in canine and rat heart failure models (Ide et al 2001; Marin‐Garcia et al 2001).…”

Tachycardia‐Induced Cardiomyopathy: A Review of Literature

“…52 Reduced tubulin mRNA and free and polymerized tubulin levels have been observed in dogs with tachycardia-induced cardiomyopathy. 53 Heinke et al 54 stimulated canine hearts at 245 bpm for 4 weeks and then at 190 bpm, and studied protein patterns of LV from the paced myocardium with controls. Elongation factor Tu was present only in the control hearts.…”

Two-dimensional gel electrophoresis image registration using block-matching techniques and deformation models

“…The conducted tests correspond to intergroup comparisons with 1024 × 1024 8-bit images, and 2D protein separation patterns were visualized by silver staining using standard protocols [48] and [49].…”