Journal article
Global Proteomics and Pathway Analysis of Pressure-overload Induced Heart Failure and Its Attenuation by Mitochondrial Targeted Peptides
Circulation. Heart failure, Vol.6(5), pp.1067-1076
09/01/2013
DOI: 10.1161/CIRCHEARTFAILURE.113.000406
PMCID: PMC3856238
PMID: 23935006
Abstract
Background: We investigated the protective effects of mitochondrial-targeted antioxidant and protective peptides, Szeto-Schiller (SS) 31 and SS20, on cardiac function, proteomic remodeling, and signaling pathways.
Methods and results: We applied an improved label-free shotgun proteomics approach to evaluate the global proteomics changes in transverse aortic constriction (TAC)-induced heart failure and the associated signaling pathway changes using ingenuity pathway analysis. We found that 538 proteins significantly changed after TAC, which mapped to 53 pathways. The top pathways were in the categories of actin cytoskeleton, mitochondrial function, intermediate metabolism, glycolysis/gluconeogenesis, and citrate cycle. Concomitant treatment with SS31 ameliorated the congestive heart failure phenotypes and mitochondrial damage induced by TAC, in parallel with global attenuation of mitochondrial proteome changes, with an average of 84% protection of mitochondrial and 69% of nonmitochondrial protein changes. This included significant amelioration of all the ingenuity pathway analysis noted above. SS20 had only modest effects on heart failure and this tracked with only partial attenuation of global proteomics changes; furthermore, actin cytoskeleton pathways were significantly protected in SS20, whereas mitochondrial and metabolic pathways essentially were not.
Conclusions: This study elucidates the signaling pathways significantly changed in pressure-overload-induced heart failure. The global attenuation of TAC-induced proteomic alterations by the mitochondrial-targeted peptide SS31 suggests that perturbed mitochondrial function may be an upstream signal to many of the pathway alterations in TAC and supports the potential clinical application of mitochondrial-targeted peptide drugs for the treatment heart failure.
Details
- Title: Subtitle
- Global Proteomics and Pathway Analysis of Pressure-overload Induced Heart Failure and Its Attenuation by Mitochondrial Targeted Peptides
- Creators
- Dao-Fu Dai - Department of Pathology, University of Washington, 1959 NE Pacific Ave, Seattle, Washington 98195, USAEdward J Hsieh - Department of Genome Sciences, University of Washington, 1959 NE Pacific Ave, Seattle, Washington 98195, USATony Chen - Department of Pathology, University of Washington, 1959 NE Pacific Ave, Seattle, Washington 98195, USALorena G Menendez - Department of Anesthesiology, University of Washington, 1959 NE Pacific Ave, Seattle, Washington 98195, USANathan B Basisty - Department of Pathology, University of Washington, 1959 NE Pacific Ave, Seattle, Washington 98195, USALauren Tsai - Department of Pathology, University of Washington, 1959 NE Pacific Ave, Seattle, Washington 98195, USARichard P Beyer - Department of Environmental Health and Biostatistics, University of Washington, 1959 NE Pacific Ave, Seattle, Washington 98195, USADavid A Crispin - Department of Pathology, University of Washington, 1959 NE Pacific Ave, Seattle, Washington 98195, USANicholas J Shulman - Department of Genome Sciences, University of Washington, 1959 NE Pacific Ave, Seattle, Washington 98195, USAHazel H Szeto - Department of Pharmacology, Weill Cornell Medical College, New York, NYRong Tian - Department of Anesthesiology, University of Washington, 1959 NE Pacific Ave, Seattle, Washington 98195, USAMichael J MacCoss - Department of Genome Sciences, University of Washington, 1959 NE Pacific Ave, Seattle, Washington 98195, USAPeter S Rabinovitch - Department of Pathology, University of Washington, 1959 NE Pacific Ave, Seattle, Washington 98195, USA
- Resource Type
- Journal article
- Publication Details
- Circulation. Heart failure, Vol.6(5), pp.1067-1076
- DOI
- 10.1161/CIRCHEARTFAILURE.113.000406
- PMID
- 23935006
- PMCID
- PMC3856238
- ISSN
- 1941-3289
- eISSN
- 1941-3297
- Grant note
- P01 AG001751 || AG / National Institute on Aging : NIA P30 AG013280 || AG / National Institute on Aging : NIA R01 HL101186 || HL / National Heart, Lung, and Blood Institute : NHLBI
- Language
- English
- Date published
- 09/01/2013
- Academic Unit
- Pathology; Iowa Neuroscience Institute; Radiation Oncology
- Record Identifier
- 9984047796602771
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