Liu Xuhan, Zhang Liping, Zhang Weihua
Department of Cardiovascular Medicine, The First Hospital of Jilin University, Changchun, China.
Front Cardiovasc Med. 2022 Aug 26;9:957524. doi: 10.3389/fcvm.2022.957524. eCollection 2022.
Pulmonary arterial hypertension, or PAH, is a condition that is characterized by pulmonary artery pressures above 20 mmHg (at rest). In the treatment of PAH, the pulmonary vascular system is regulated to ensure a diastolic and contraction balance; nevertheless, this treatment does not prevent or reverse pulmonary vascular remodeling and still causes pulmonary hypertension to progress. According to Warburg, the link between metabolism and proliferation in PAH is similar to that of cancer, with a common aerobic glycolytic phenotype. By activating HIF, aerobic glycolysis is enhanced and cell proliferation is triggered. Aside from glutamine metabolism, the Randle cycle is also present in PAH. Enhanced glutamine metabolism replenishes carbon intermediates used by glycolysis and provides energy to over-proliferating and anti-apoptotic pulmonary vascular cells. By activating the Randle cycle, aerobic oxidation is enhanced, ATP is increased, and myocardial injury is reduced. PAH is predisposed by epigenetic dysregulation of DNA methylation, histone acetylation, and microRNA. This article discusses the abnormal metabolism of PAH and how metabolic therapy can be used to combat remodeling.
肺动脉高压（PAH）是一种以静息时肺动脉压高于20 mmHg为特征的病症。在PAH的治疗中，肺血管系统会得到调节以确保舒张和收缩平衡；然而，这种治疗并不能预防或逆转肺血管重塑，仍会导致肺动脉高压进展。根据瓦尔堡的理论，PAH中代谢与增殖之间的联系类似于癌症，具有共同的有氧糖酵解表型。通过激活低氧诱导因子（HIF），有氧糖酵解增强，细胞增殖被触发。除了谷氨酰胺代谢外，兰德尔循环也存在于PAH中。增强的谷氨酰胺代谢补充了糖酵解所使用的碳中间体，并为过度增殖和抗凋亡的肺血管细胞提供能量。通过激活兰德尔循环，有氧氧化增强，三磷酸腺苷（ATP）增加，心肌损伤减轻。PAH由DNA甲基化、组蛋白乙酰化和微小RNA的表观遗传失调引发。本文讨论了PAH的异常代谢以及如何利用代谢疗法对抗重塑。
