Proteomic Analysis of Atrial Appendages Revealed the Pathophysiological Changes of Atrial Fibrillation

doi:10.3389/fphys.2020.573433

. 2020 Sep 16:11:573433.

doi: 10.3389/fphys.2020.573433. eCollection 2020.

Proteomic Analysis of Atrial Appendages Revealed the Pathophysiological Changes of Atrial Fibrillation

Ban Liu¹, Xiang Li², Cuimei Zhao³, Yuliang Wang⁴, Mengwei Lv^{5

6}, Xin Shi⁷, Chunyan Han¹, Pratik Pandey¹, Chunhua Qian⁸, Changfa Guo⁹, Yangyang Zhang⁶

Affiliations

¹ Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
² Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China.
³ Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
⁴ Department of Immunology, School of Basic Medical Science, Nanjing Medical University, Nanjing, China.
⁵ Shanghai East Hospital of Clinical Medical College, Nanjing Medical University, Shanghai, China.
⁶ Department of Cardiovascular Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
⁷ Department of Pediatric Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁸ Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
⁹ Department of Cardiovascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

PMID: 33041871
PMCID: PMC7526521
DOI: 10.3389/fphys.2020.573433

Proteomic Analysis of Atrial Appendages Revealed the Pathophysiological Changes of Atrial Fibrillation

Ban Liu et al. Front Physiol. 2020.

. 2020 Sep 16:11:573433.

doi: 10.3389/fphys.2020.573433. eCollection 2020.

Authors

Ban Liu¹, Xiang Li², Cuimei Zhao³, Yuliang Wang⁴, Mengwei Lv^{5

6}, Xin Shi⁷, Chunyan Han¹, Pratik Pandey¹, Chunhua Qian⁸, Changfa Guo⁹, Yangyang Zhang⁶

Affiliations

¹ Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
² Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China.
³ Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
⁴ Department of Immunology, School of Basic Medical Science, Nanjing Medical University, Nanjing, China.
⁵ Shanghai East Hospital of Clinical Medical College, Nanjing Medical University, Shanghai, China.
⁶ Department of Cardiovascular Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
⁷ Department of Pediatric Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁸ Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
⁹ Department of Cardiovascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

PMID: 33041871
PMCID: PMC7526521
DOI: 10.3389/fphys.2020.573433

Abstract

Atrial fibrillation (AF), known as the most common arrhythmia in the developed world, affects 1.5-2.0% of the population. Numerous basic studies have been carried out to identify the roles of electric and structural remodeling in the pathophysiological changes of AF, but more explorations are required to further understand the mechanisms of AF development. Proteomics enables researchers to identify protein alterations responsible for the pathological developing progresses of diseases. Compared to the genome, the proteome is closely related to the disease phenotype and can better manifest the progression of diseases. In this study, AF patients proteomically analyzed to identify possible mechanisms. Totally 20 patients undergoing cardiac surgery (10 with paroxysmal AF and 10 with persistent AF) and 10 healthy subjects were recruited. The differentially expressed proteins identified here included AKR1A1, LYZ, H2AFY, DDAH1, FGA, FGB, LAMB1, LAMC1, MYL2, MYBPC3, MYL5, MYH10, HNRNPU, DKK3, COPS7A, YWHAQ, and PAICS. These proteins were mainly involved in the development of structural remodeling. The differently expressed proteins may provide a new perspective for the pathological process of AF, and may enable useful targets for drug interference. Nevertheless, more research in terms of multi-omics is required to investigate possible implicated molecular pathways of AF development.

Keywords: atrial fibrillation; mechanism; proteins; proteomics; structural remodeling.

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Figures

**FIGURE 1**
Heatmap visualization of the differently expressed proteins identified in healthy controls, paroxysmal AF patients, and permanent AF patients. **(A)** Heatmap showing the differential protein expression profiles compared in pairs among three groups. **(B)** The differently expressed proteins identified in three groups by Venn diagram via comparing in pairs.

**FIGURE 2**
The protein-protein interaction network for the 17 identified proteins.

**FIGURE 3**
GO analysis of differently expressed proteins in AF patients. **(A)** molecular function, **(B)** biological process, and **(C)** cell components.

See this image and copyright information in PMC

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References

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[1] Bongini C., Ferrantini C., Girolami F., Coppini R., Arretini A., Targetti M., et al. (2016). Impact of genotype on the occurrence of atrial fibrillation in patients with hypertrophic cardiomyopathy. Am. J. Cardiol. 117 1151–1159. 10.1016/j.amjcard.2015.12.058 - DOI - PubMed

[2] Bongini C., Ferrantini C., Girolami F., Coppini R., Arretini A., Targetti M., et al. (2016). Impact of genotype on the occurrence of atrial fibrillation in patients with hypertrophic cardiomyopathy. Am. J. Cardiol. 117 1151–1159. 10.1016/j.amjcard.2015.12.058 - DOI - PubMed

[3] Choe C. U., Schulze-Bahr E., Neu A., Xu J., Zhu Z. I., Sauter K., et al. (2006). C-terminal HERG (LQT2) mutations disrupt IKr channel regulation through 14-3-3epsilon. Hum. Mol. Genet. 15 2888–2902. 10.1093/hmg/ddl230 - DOI - PubMed

[4] Choe C. U., Schulze-Bahr E., Neu A., Xu J., Zhu Z. I., Sauter K., et al. (2006). C-terminal HERG (LQT2) mutations disrupt IKr channel regulation through 14-3-3epsilon. Hum. Mol. Genet. 15 2888–2902. 10.1093/hmg/ddl230 - DOI - PubMed

[5] Cotrufo M., De Santo L., Della Corte A., Di Meglio F., Guerra G., Quarto C., et al. (2005). Basal lamina structural alterations in human asymmetric aneurismatic aorta. Eur. J. Histochem. [EJH] 49 363–370. 10.4081/964 - DOI - PubMed

[6] Cotrufo M., De Santo L., Della Corte A., Di Meglio F., Guerra G., Quarto C., et al. (2005). Basal lamina structural alterations in human asymmetric aneurismatic aorta. Eur. J. Histochem. [EJH] 49 363–370. 10.4081/964 - DOI - PubMed

[7] Frustaci A., Chimenti C., Bellocci F., Morgante E., Russo M. A., Maseri A. (1997). Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation 96 1180–1184. 10.1161/01.cir.96.4.1180 - DOI - PubMed

[8] Frustaci A., Chimenti C., Bellocci F., Morgante E., Russo M. A., Maseri A. (1997). Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation 96 1180–1184. 10.1161/01.cir.96.4.1180 - DOI - PubMed

[9] Haque N., Ouda R., Chen C., Ozato K., Hogg J. R. (2018). ZFR coordinates crosstalk between RNA decay and transcription in innate immunity. Nat. Commun. 9:1145. - PMC - PubMed

[10] Haque N., Ouda R., Chen C., Ozato K., Hogg J. R. (2018). ZFR coordinates crosstalk between RNA decay and transcription in innate immunity. Nat. Commun. 9:1145. - PMC - PubMed

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Proteomic Analysis of Atrial Appendages Revealed the Pathophysiological Changes of Atrial Fibrillation

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Proteomic Analysis of Atrial Appendages Revealed the Pathophysiological Changes of Atrial Fibrillation

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