临床儿科杂志 ›› 2026, Vol. 44 ›› Issue (3): 222-228.doi: 10.12372/jcp.2026.25e1431

• 论著 • 上一篇    下一篇

基于磷酸化蛋白质组学的主动脉狭窄血管重塑中GORASP1功能机制探索

刘悦1, 石海群1, 孙欣1, 赵瑞1, 石彦1, 蔡科1, 敖俊杰1, 陈伟呈2, 赵健元1   

  1. 1.上海交通大学医学院附属新华医院 心血管发育与再生医学研究所 环境与儿童健康教育部和上海市重点实验室 (上海 200092)
    2.复旦大学附属儿科医院心胸外科 国家儿童医学中心 国家卫生健康委员会新生儿疾病重点实验室 (上海 201102)
  • 收稿日期:2025-11-17 录用日期:2025-12-31 出版日期:2026-03-15 发布日期:2026-03-06

Exploration of the functional mechanism of GORASP1 in vascular remodeling of aortic coarctation based on phosphoproteomics

LIU Yue1, SHI Haiqun1, SUN Xin1, ZHAO Rui1, SHI Yan1, CAI Ke1, AO Junjie1, CHEN Weicheng2, ZHAO Jianyuan1   

  1. 1. Institute of Cardiovascular Development and Regeneration, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; Key Laboratory of Environment and Child Health, Ministry of Education and Shanghai Municipality, Shanghai 200092, China
    2. Department of Cardiothoracic Surgery, Children's Hospital of Fudan University; National Children's Medical Center; NHC Key Laboratory of Neonatal Diseases, Shanghai 201102, China
  • Received:2025-11-17 Accepted:2025-12-31 Published:2026-03-15 Online:2026-03-06

摘要:

目的 基于磷酸化蛋白质组学筛选主动脉狭窄(CoA)血管重塑中的关键磷酸化蛋白,探讨高尔基体蛋白GORASP1在CoA发病机制中的作用。方法 收集5对CoA患者狭窄组织及对照组织(正常主动脉组织),采用磷酸化蛋白质组学技术筛选差异磷酸化蛋白。通过生物信息学分析明确差异蛋白的功能,阐明GORASP1参与CoA疾病的分子机制。结果 对CoA组与对照组的差异蛋白质功能分析发现,其显著富集于氧化应激、能量代谢等通路,提示这些生物学过程在CoA病理机制中扮演重要角色。其中,尤为值得关注的是,被鉴定为最显著差异磷酸化蛋白的GORASP1,其功能主要涉及高尔基体组织和自噬通路,这表明GORASP1可能是连接上述共性病理过程与细胞器功能紊乱的一个关键节点分子。结论 CoA特异的磷酸化修饰特征与氧化应激密切相关,GORASP1可能通过调控细胞器功能和自噬过程参与血管重塑,为CoA的机制研究和治疗靶点开发提供了新方向。

关键词: 主动脉狭窄, 磷酸化修饰, 血管重塑, 机制探讨

Abstract:

Objective To screen key phosphorylated proteins involved in vascular remodeling of aortic coarctation (CoA) using phosphoproteomics and to investigate the role of the Golgi protein GORASP1 in its pathogenesis. Methods Paired tissue samples from CoA stenotic segments and control aortic tissues (n=5 pairs) were collected. Differentially phosphorylated proteins were identified through phosphoproteomic profiling. Bioinformatics analyses were performed to elucidate the functions of these proteins and delineate the mechanism by which GORASP1 contributes to CoA. Results Functional analysis of the differential proteins between the CoA and control groups revealed significant enrichment in pathways such as oxidative stress and energy metabolism, suggesting these biological processes play important roles in CoA pathology. Notably, GORASP1 was identified as the most significantly differentially phosphorylated protein. Its functions were primarily associated with Golgi organization and the autophagy pathway, suggesting that GORASP1 may act as a key nodal molecule linking these common pathological processes to organelle dysfunction. Conclusion The specific phosphorylation signature in CoA is closely related to oxidative stress. GORASP1 likely participates in vascular remodeling by regulating organelle function and autophagy processes, providing new directions for mechanistic research and therapeutic target development in CoA.

Key words: aortic coarctation, phosphorylation modification, vascular remodeling, mechanistic investigation

中图分类号: 

  • R72