کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10953998 | 1097829 | 2010 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Proteomic and metabolomic analysis of atrial profibrillatory remodelling in congestive heart failure
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Proteomic and metabolomic analysis of atrial profibrillatory remodelling in congestive heart failure Proteomic and metabolomic analysis of atrial profibrillatory remodelling in congestive heart failure](/preview/png/10953998.png)
چکیده انگلیسی
Congestive heart failure (CHF) leads to atrial structural remodelling and increased susceptibility to atrial fibrillation. The underlying molecular mechanisms are poorly understood. We applied high-throughput proteomic and metabolomic analysis to left-atrial cardiomyocytes and tissues obtained from sham and ventricular-tachypaced (VTP, 240 bpm Ã 24 h and Ã 2 weeks) CHF dogs. Protein-extracts were subjected to two-dimensional gel electrophoresis using differential in-gel electrophoresis technology. Differentially expressed (P < 0.05) proteins were identified by tandem mass-spectrometry. Cardiac metabolites were assayed with high-resolution NMR spectroscopy. Extensive changes occurred in structural proteins, particularly at 2-week VTP, with desmin and filamin fragmentation suggesting structural damage, which was confirmed by electron-microscopy. Oxidant stress was evidenced by decreased antioxidant proteins (superoxide dismutase and peroxiredoxin) at 2-week VTP. Extensive changes in cardioprotective heat shock proteins (HSPs) occurred, with several proteins increasing rapidly (HSP27, HSP60 and HSP70) and others showing a delayed rise (GRP78, α-B-crystallin, and HSP90). An evolving adaptive response to metabolic stress was suggested by early upregulation of malate dehydrogenase (DH), α-/β-enolase and pyruvate dehydrogenase (α-subunit of E1 component) and delayed downregulation of a host of enzymes, along with extensive metabolomic changes. Early changes in metabolite expression that persisted as CHF developed included increased concentrations of glucose and alanine. ADP/ATP accumulation and alpha-ketoisovalerate depletion at 2-week VTP suggested a combination of metabolic stress and less effective energy utilization, as well as a shift from glycolysis to alpha-ketoacid metabolism. We conclude that VTP-induced CHF causes time-dependent changes in the atrial proteome and metabolome, providing insights into molecular mechanisms contributing to arrhythmogenic atrial remodelling.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 49, Issue 5, November 2010, Pages 851-863
Journal: Journal of Molecular and Cellular Cardiology - Volume 49, Issue 5, November 2010, Pages 851-863
نویسندگان
Ayesha I. De Souza, Sophie Cardin, Robin Wait, Yuen-Li Chung, Meeraa Vijayakumar, Ange Maguy, A. John Camm, Stanley Nattel,