2. Academic Validation
  3. Plasma Proteomic Profiling Reveals ITGA2B as A Key Regulator of Heart Health in High-altitude Settlers

Plasma Proteomic Profiling Reveals ITGA2B as A Key Regulator of Heart Health in High-altitude Settlers

  • Genomics Proteomics Bioinformatics. 2025 Apr 8:qzaf030. doi: 10.1093/gpbjnl/qzaf030.
Yihao Wang 1,  Pan Shen 1,  Zhenhui Wu 1 2,  Bodan Tu 1 2,  Cheng Zhang 1 3,  Yongqiang Zhou 1,  Yisi Liu 4,  Guibin Wang 5,  Zhijie Bai 1,  Xianglin Tang 1,  Chengcai Lai 1,  Haitao Lu 6 7,  Wei Zhou 1,  Yue Gao 1 2 3 8
Affiliations

Affiliations

  • 1 Beijing Institute of Radiation Medicine, Beijing 100850, China.
  • 2 School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330000, China.
  • 3 School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
  • 4 School of Nursing, Capital Medical University, Beijing 100069, China.
  • 5 State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China.
  • 6 School of Chinese Medicine, Hong Kong Traditional Chinese Medicine Phenome Research Center, Hong Kong Baptist University, Hong Kong Special Administrative Region 999077, China.
  • 7 Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai 200240, China.
  • 8 Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China.
PMID: 40198259 DOI: 10.1093/gpbjnl/qzaf030
Abstract

Myocardial injury is a common disease in the plateau, especially in the lowlanders who have migrated to the plateau, in which the pathogenesis is not well understood. Here, we established a cohort of lowlanders comprising individuals from both low-altitude and high-altitude areas and conducted plasma proteome profiling. Proteomic data showed that there was a significant shift in energy metabolism and inflammatory response in individuals with myocardial abnormalities at high altitude. Notably, Integrin ITGA2B emerged as a potential key player in this context. Functional studies demonstrated that ITGA2B upregulated the transcription and secretion of interleukin-6 (IL-6) through integrin-linked kinase (ILK) and nuclear factor-κB (NF-κB) signaling axis under hypoxic conditions. Moreover, ITGA2B disrupted mitochondrial structure and function, increased glycolytic capacity, and aggravated energy reprogramming from Oxidative Phosphorylation to glycolysis. Leveraging the therapeutic potential of traditional Chinese medicine in cardiac diseases, we discovered that tanshinone ⅡA (TanⅡA) effectively alleviated the high-altitude myocardial injury caused by the abnormally elevated expression of ITGA2B, thus providing a novel candidate therapeutic strategy for the prevention and treatment of high-altitude myocardial injury.

Keywords

High-altitude settlers; ITGA2B; Myocardial injury; Plasma proteome; TanⅡA.

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