Wang Yihao, Shen Pan, Wu Zhenhui, Tu Bodan, Zhang Cheng, Zhou Yongqiang, Liu Yisi, Wang Guibin, Bai Zhijie, Tang Xianglin, Lai Chengcai, Lu Haitao, Zhou Wei, Gao Yue
Beijing Institute of Radiation Medicine, Beijing 100850, China.
School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330000, China.
Genomics Proteomics Bioinformatics. 2025 Apr 8. doi: 10.1093/gpbjnl/qzaf030.
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.
心肌损伤是高原地区的一种常见疾病，尤其是在移居到高原的低海拔地区人群中，其发病机制尚不清楚。在此，我们建立了一个由来自低海拔和高海拔地区个体组成的低海拔人群队列，并进行了血浆蛋白质组分析。蛋白质组学数据显示，高海拔地区心肌异常个体的能量代谢和炎症反应发生了显著变化。值得注意的是，整合素ITGA2B在这种情况下成为一个潜在的关键因素。功能研究表明，在缺氧条件下，ITGA2B通过整合素连接激酶（ILK）和核因子-κB（NF-κB）信号轴上调白细胞介素-6（IL-6）的转录和分泌。此外，ITGA2B破坏线粒体结构和功能，增加糖酵解能力，并加剧从氧化磷酸化到糖酵解的能量重编程。利用中药在心脏病治疗中的潜在作用，我们发现丹参酮ⅡA（TanⅡA）有效减轻了由ITGA2B异常高表达引起的高原心肌损伤，从而为高原心肌损伤的防治提供了一种新的候选治疗策略。
