Cardiac Proteome Profiling in Ischemic and Dilated Cardiomyopathy Mouse Models
Heart failure (HF) is a worldwide pandemic with an unacceptable high level of morbidity and mortality. Understanding the different pathophysiological mechanisms will contribute to prevention and individualized therapy of HF. We established mouse models for ischemic cardiomyopathy (ICM) and dilated c...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-06-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2019.00750/full |
| _version_ | 1811273992827305984 |
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| author | Danbo Lu Yan Xia Zhangwei Chen Ao Chen Yuan Wu Jianguo Jia Aijun Sun Yunzeng Zou Juying Qian Junbo Ge |
| author_facet | Danbo Lu Yan Xia Zhangwei Chen Ao Chen Yuan Wu Jianguo Jia Aijun Sun Yunzeng Zou Juying Qian Junbo Ge |
| author_sort | Danbo Lu |
| collection | DOAJ |
| description | Heart failure (HF) is a worldwide pandemic with an unacceptable high level of morbidity and mortality. Understanding the different pathophysiological mechanisms will contribute to prevention and individualized therapy of HF. We established mouse models for ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) by inducing myocardial infarction (MI) and Coxsackievirus B3 infection, respectively. Isobaric tags for relative and absolute quantitation and liquid chromatography coupled with tandem mass spectrometry technology was used to identify the protein expression profiles in control and failing hearts. A total of 1,638 proteins were identified and compared in this proteomics analysis. Among them, 286 proteins were differently expressed. Gene ontology, KEGG pathway and ingenuity pathway analysis was performed to systematically assess the potential connections of the differentially expressed proteins to biological functions. Compared with control group, the differentially expressed proteins derived from the hearts of ICM and DCM mice were partially similar and mainly modulated in oxidative phosphorylation, metabolism and protein folding pathways. Moreover, difference still existed, the differentially expressed proteins between DCM and ICM hearts were significantly modulated in oxidative phosphorylation, metabolic and AMPK signaling pathways. Confirmatory western bolt analysis demonstrated that SDHB was down-regulated in both ICM and DCM hearts, while UQCRQ, GLUT4 and adiponectin were up-regulated in ICM hearts. Adenosine triphosphate (ATP) concentration significantly decreased in both DCM and ICM hearts. The protein expression of phospho-AMPKα decreased significantly in DCM hearts, but increased in ICM. In summary, oxidative phosphorylation, cardiac metabolism, and protein folding play critical roles in the pathogenesis of HF. The diverse changes in protein expression profiles between failing hearts induced by either MI or CVB3 infection demonstrated the heterogeneity of HF. Understanding the differences in proteome profiles could offer more precise therapeutic options for HF. |
| first_indexed | 2024-04-12T23:10:46Z |
| format | Article |
| id | doaj.art-965a26a676a843d89b7251d6b8030753 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-12T23:10:46Z |
| publishDate | 2019-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-965a26a676a843d89b7251d6b80307532022-12-22T03:12:49ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2019-06-011010.3389/fphys.2019.00750451716Cardiac Proteome Profiling in Ischemic and Dilated Cardiomyopathy Mouse ModelsDanbo LuYan XiaZhangwei ChenAo ChenYuan WuJianguo JiaAijun SunYunzeng ZouJuying QianJunbo GeHeart failure (HF) is a worldwide pandemic with an unacceptable high level of morbidity and mortality. Understanding the different pathophysiological mechanisms will contribute to prevention and individualized therapy of HF. We established mouse models for ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) by inducing myocardial infarction (MI) and Coxsackievirus B3 infection, respectively. Isobaric tags for relative and absolute quantitation and liquid chromatography coupled with tandem mass spectrometry technology was used to identify the protein expression profiles in control and failing hearts. A total of 1,638 proteins were identified and compared in this proteomics analysis. Among them, 286 proteins were differently expressed. Gene ontology, KEGG pathway and ingenuity pathway analysis was performed to systematically assess the potential connections of the differentially expressed proteins to biological functions. Compared with control group, the differentially expressed proteins derived from the hearts of ICM and DCM mice were partially similar and mainly modulated in oxidative phosphorylation, metabolism and protein folding pathways. Moreover, difference still existed, the differentially expressed proteins between DCM and ICM hearts were significantly modulated in oxidative phosphorylation, metabolic and AMPK signaling pathways. Confirmatory western bolt analysis demonstrated that SDHB was down-regulated in both ICM and DCM hearts, while UQCRQ, GLUT4 and adiponectin were up-regulated in ICM hearts. Adenosine triphosphate (ATP) concentration significantly decreased in both DCM and ICM hearts. The protein expression of phospho-AMPKα decreased significantly in DCM hearts, but increased in ICM. In summary, oxidative phosphorylation, cardiac metabolism, and protein folding play critical roles in the pathogenesis of HF. The diverse changes in protein expression profiles between failing hearts induced by either MI or CVB3 infection demonstrated the heterogeneity of HF. Understanding the differences in proteome profiles could offer more precise therapeutic options for HF.https://www.frontiersin.org/article/10.3389/fphys.2019.00750/fullheart failureischemic cardiomyopathydilated cardiomyopathyproteomicsmetabolism |
| spellingShingle | Danbo Lu Yan Xia Zhangwei Chen Ao Chen Yuan Wu Jianguo Jia Aijun Sun Yunzeng Zou Juying Qian Junbo Ge Cardiac Proteome Profiling in Ischemic and Dilated Cardiomyopathy Mouse Models Frontiers in Physiology heart failure ischemic cardiomyopathy dilated cardiomyopathy proteomics metabolism |
| title | Cardiac Proteome Profiling in Ischemic and Dilated Cardiomyopathy Mouse Models |
| title_full | Cardiac Proteome Profiling in Ischemic and Dilated Cardiomyopathy Mouse Models |
| title_fullStr | Cardiac Proteome Profiling in Ischemic and Dilated Cardiomyopathy Mouse Models |
| title_full_unstemmed | Cardiac Proteome Profiling in Ischemic and Dilated Cardiomyopathy Mouse Models |
| title_short | Cardiac Proteome Profiling in Ischemic and Dilated Cardiomyopathy Mouse Models |
| title_sort | cardiac proteome profiling in ischemic and dilated cardiomyopathy mouse models |
| topic | heart failure ischemic cardiomyopathy dilated cardiomyopathy proteomics metabolism |
| url | https://www.frontiersin.org/article/10.3389/fphys.2019.00750/full |
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