Tandem mass tag-based quantitative proteomic analysis identification of succinylation related proteins in pathogenesis of thoracic aortic aneurysm and aortic dissection

Yu Zhang; Hongwei Zhang; Haiyue Wang; Chenhao Wang; Peng Yang; Chen Lu; Yu Liu; Zhenyuan Xu; Yi Xie; Jia Hu

doi:10.7717/peerj.15258

Tandem mass tag-based quantitative proteomic analysis identification of succinylation related proteins in pathogenesis of thoracic aortic aneurysm and aortic dissection

PeerJ. 2023 May 11:11:e15258. doi: 10.7717/peerj.15258. eCollection 2023.

Authors

Yu Zhang^#¹, Hongwei Zhang^#^{1

2}, Haiyue Wang¹, Chenhao Wang¹, Peng Yang¹, Chen Lu¹, Yu Liu¹, Zhenyuan Xu¹, Yi Xie¹, Jia Hu^{1

2

3}

Affiliations

¹ Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, China.
² Department of Cardiovascular Surgery, Guang'an Hospital of West China Hospital of Sichuan University, Guang'an, China.
³ Cardiovascular Surgery Research Laboratory, West China Hospital, Sichuan University, Chengdu, China.

^# Contributed equally.

Abstract

Background: Thoracic aortic aneurysm and dissection (TAAD) are devastating cardiovascular diseases with a high rate of disability and mortality. Lysine succinylation, a newly found post-translational modification, has been reported to play an important role in cardiovascular diseases. However, how succinylation modification influences TAAD remains obscure.

Methods: Ascending aortic tissues were obtained from patients with thoracic aortic aneurysm (TAA, n = 6), thoracic aortic dissection (TAD) with pre-existing aortic aneurysm (n = 6), and healthy subjects (n = 6). Global lysine succinylation level was analyzed by Western blotting. The differentially expressed proteins (DEPs) were analyzed by tandem mass tag (TMT) labeling and mass spectrometry. Succinylation-related proteins selected from the literature review and AmiGO database were set as a reference inventory for further analysis. Then, the pathological aortic sections were chosen to verify the proteomic results by Western blotting and qRT-PCR.

Results: The level of global lysine succinylation significantly increased in TAA and TAD patients compared with healthy subjects. Of all proteins identified by proteomic analysis, 197 common DEPs were screened both in TAA and TAD group compared with the control group, of which 93 proteins were significantly upregulated while 104 were downregulated. Among these 197 DEPs, OXCT1 overlapped with the succinylation-related proteins and was selected as the target protein involved in thoracic aortic pathogenesis. OXCT1 was further verified by Western blotting and qRT-PCR, and the results showed that OXCT1 in TAA and TAD patients was significantly lower than that in healthy donors (p < 0.001), which was consistent with the proteomic results.

Conclusions: OXCT1 represents novel biomarkers for lysine succinylation of TAAD and might be a therapeutic target in the future.

Keywords: OXCT1; Proteomics; Succinylation; Tandem mass tag labelling; Thoracic aortic aneurysm; Thoracic aortic dissection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aortic Aneurysm*
Aortic Aneurysm, Thoracic* / diagnosis
Aortic Dissection*
Humans
Lysine
Proteomics / methods

Substances

Lysine
1,3,4,6-tetra-O-acetyl-2-azido-2-deoxyglucopyranose

Grants and funding

This study was supported by the National Natural Science Foundation of China (No. 81670327); the Sichuan Science and Technology Program (2019YJ0046, 2018SZ0384); the 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University (No. 2020HXJS015); the 1·3·5 project for disciplines of excellence–Clinical Research Incubation Project, West China Hospital, Sichuan University (No. 2019HXFH027); and the Project of China International Medical Foundation (Z-2016-23-2101-27). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.