生物能学
下调和上调
转酮酶
磷酸戊糖途径
糖酵解
碳水化合物代谢
厌氧糖酵解
癌症研究
化学
线粒体
生物
新陈代谢
细胞生物学
生物化学
酶
基因
作者
C Wang,Li Zhang,Qinghua Zhang,Hui Zheng,Yang Xi,Weixing Cai,Qiuying Zou,Jie Lin,Lin Zhang,Lin Zhong,Xinyao Li,Youhao Liao,Qin Liu,Liangwan Chen,Yumei Li
摘要
Abstract Aim Aortic dissection (AD) is a disease with rapid onset but with no effective therapeutic drugs yet. Previous studies have suggested that glucose metabolism plays a critical role in the progression of AD. Transketolase (TKT) is an essential bridge between glycolysis and the pentose phosphate pathway. However, its role in the development of AD has not yet been elucidated. In this study, we aimed to explore the role of TKT in AD. Methods We collected AD patients' aortic tissues and used high‐throughput proteome sequencing to analyze the main factors influencing AD development. We generated an AD model using BAPN in combination with angiotensin II (Ang II) and pharmacological inhibitors to reduce TKT expression. The effects of TKT and its downstream mediators on AD were elucidated using human aortic vascular smooth muscle cells (HAVSMCs). Results We found that glucose metabolism plays an important role in the development of AD and that TKT is upregulated in patients with AD. Western blot and immunohistochemistry confirmed that TKT expression was upregulated in mice with AD. Reduced TKT expression attenuated AD incidence and mortality, maintained the structural integrity of the aorta, aligned elastic fibers, and reduced collagen deposition. Mechanistically, TKT was positively associated with impaired mitochondrial bioenergetics by upregulating AKT/MDM2 expression, ultimately contributing to NDUFS1 downregulation. Conclusion Our results provide new insights into the role of TKT in mitochondrial bioenergetics and AD progression. These findings provide new intervention options for the treatment of AD.
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