Key result
Naturally occurring and induced dilated cardiomyopathy in dogs significantly altered the expression of 40 heart mitochondrial proteins, predominantly those involved in oxidative phosphorylation, compared to healthy controls.
p-value: p=<0.05
Canine models of naturally occurring and induced DCM show significant alterations in heart mitochondrial proteins related to oxidative phosphorylation dysfunction.
Mitochondrial protein changes in canine DCM models are hypothesis-generating; leaves open relevance to human disease mechanisms or therapy.
OBJECTIVE: To map canine mitochondrial proteins and identify qualitative and quantitative differences in heart mitochondrial protein expression between healthy dogs and dogs with naturally occurring and induced dilated cardiomyopathy (DCM). SAMPLE POPULATION: Left ventricle samples were obtained from 7 healthy dogs, 7 Doberman Pinschers with naturally occurring DCM, and 7 dogs with induced DCM. PROCEDURES: Fresh and frozen mitochondrial fractions were isolated from the left ventricular free wall and analyzed by 2-dimensional electrophoresis. Protein spots that increased or decreased in density by >or= 2-fold between groups were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or quadrupole selecting, quadrupole collision cell, time-of-flight mass spectrometry. RESULTS: Within narrow pH gradients of control canine heart mitochondrial samples, a total of 1,528 protein spots were revealed. Forty subunits of heart mitochondrial proteins that differ significantly from control tissues were altered in tissue specimens from dogs with naturally occurring and induced forms of DCM. The most affected heart mitochondrial proteins in both groups were those of oxidative phosphorylation (55%). Upregulation of manganese superoxide dismutase was suggestive of heart oxidative injury in tissue specimens from dogs with both forms of DCM. Evidence of apoptosis was associated with overexpression of the heart mitochondrial voltage-dependent anion channel-2 protein and endonuclease G in tissue specimens from dogs with induced DCM. CONCLUSIONS AND CLINICAL RELEVANCE: Alterations of heart mitochondrial proteins related to oxidative phosphorylation dysfunction were more prevalent in tissue specimens from dogs with induced or naturally occurring DCM, compared with those of control dogs.
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Lopes et al. (2006) studied Dilated cardiomyopathy (DCM) (n=21). Naturally occurring and induced DCM vs. Healthy control dogs was evaluated on Mitochondrial protein spots with ≥2-fold change in expression (p=<0.05). Naturally occurring and induced dilated cardiomyopathy in dogs significantly altered the expression of 40 heart mitochondrial proteins, predominantly those involved in oxidative phosphorylation, compared to healthy controls.
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