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...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 proteomic 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 alpha-Ⅱb(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 the integrin-linked kinase(ILK)/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 tanshinoneⅡA(TanⅡA)effectively alleviated the myocardial injury caused by the abnormally elevated expression of ITGA2B and hypobaric hypoxia exposure in mice,thus providing a novel candidate therapeutic strategy for the prevention and treatment of high-altitude myocardial injury.展开更多
基金supported by the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(Grant No.ZYYCXTD-D-202207)the National Natural Science Foundation of China(Grant No.82204774).
文摘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 proteomic 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 alpha-Ⅱb(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 the integrin-linked kinase(ILK)/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 tanshinoneⅡA(TanⅡA)effectively alleviated the myocardial injury caused by the abnormally elevated expression of ITGA2B and hypobaric hypoxia exposure in mice,thus providing a novel candidate therapeutic strategy for the prevention and treatment of high-altitude myocardial injury.
