Altered myofilament stoichiometry in response to heart failure in a cardioprotective α-myosin heavy chain transgenic rabbit model

Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD, USA.
PROTEOMICS - CLINICAL APPLICATIONS (Impact Factor: 2.96). 04/2011; 5(3-4):147-58. DOI: 10.1002/prca.201000116
Source: PubMed


Decreases in α myosin heavy chain (α-MHC) is a common feature of human heart failure (HF), whereas α-MHC overexpression in transgenic (TG) rabbits is cardioprotective against tachycardia-induced cardiomyopathy (TIC). Hypothesizing that MHC isoform content alterations would impact sarcomere and mitochondrial energetics protein complement, we investigated the impact of α-MHC overexpression on global cardiac protein expression.
Protein expression was assessed by two-dimensional gel electrophoresis and MS on the extracts from TG and nontransgenic (NTG) rabbits under TIC or sham-operated conditions.
We observed significant changes in the levels of actin, myosin light chain 2, and desmin between the left ventricular (LV) tissue of TG and NTG animals. The proteome was broadly impacted, with significant changes in mitochondrial energetics and chaperone protein families. No changes were observed in total cellular MHC or in myofibril-associated MHC. In myofibrils isolated from TG(sham) animals, only actin levels were altered in TG(sham) compared with NTG(sham) animals, suggesting careful myofibril assembly regulation.
These data suggest that myofibril protein composition may protect against TIC, emphasizing protein interconnectivity and demonstrating the need for broad-based proteomic studies in understanding targeted genetic manipulations. This study identifies the targets for future development of cardioprotective agents and elucidates tachycardia-induced heart failure pathways.

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Available from: David Raymond Graham, Sep 03, 2014
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