Liang Shuxin, Yegambaram Manivannan, Wang Ting, Wang Jian, Black Stephen M, Tang Haiyang
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China.
Biomedicines. 2022 Feb 1;10(2):341. doi: 10.3390/biomedicines10020341.
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevated pulmonary arterial pressure due to increased pulmonary vascular resistance, secondary to sustained pulmonary vasoconstriction and excessive obliterative pulmonary vascular remodeling. Work over the last decade has led to the identification of a critical role for metabolic reprogramming in the PAH pathogenesis. It is becoming clear that in addition to its role in ATP generation, the mitochondrion is an important organelle that regulates complex and integrative metabolic- and signal transduction pathways. This review focuses on mitochondrial metabolism alterations that occur in deranged pulmonary vessels and the right ventricle, including abnormalities in glycolysis and glucose oxidation, fatty acid oxidation, glutaminolysis, redox homeostasis, as well as iron and calcium metabolism. Further understanding of these mitochondrial metabolic mechanisms could provide viable therapeutic approaches for PAH patients.
肺动脉高压（PAH）是一种进行性疾病，其特征是由于肺血管阻力增加导致肺动脉压力升高，这继发于持续性肺血管收缩和过度的闭塞性肺血管重塑。过去十年的研究已确定代谢重编程在PAH发病机制中起关键作用。越来越清楚的是，线粒体除了在ATP生成中发挥作用外，还是一个重要的细胞器，可调节复杂的综合代谢和信号转导途径。本综述重点关注紊乱的肺血管和右心室中发生的线粒体代谢改变，包括糖酵解和葡萄糖氧化、脂肪酸氧化、谷氨酰胺分解、氧化还原稳态以及铁和钙代谢的异常。对这些线粒体代谢机制的进一步了解可为PAH患者提供可行的治疗方法。
