High Altitude Medicine Research Center (CEIMA), Arturo Prat University, Iquique 1110939, Chile.
Int J Mol Sci. 2024 Oct 14;25(20):11023. doi: 10.3390/ijms252011023.
The pathophysiology of pulmonary hypertension is complex and multifactorial. It is a disease characterized by increased pulmonary vascular resistance at the level due to sustained vasoconstriction and remodeling of the pulmonary arteries, which triggers an increase in the mean pulmonary artery pressure and subsequent right ventricular hypertrophy, which in some cases can cause right heart failure. Hypoxic pulmonary hypertension (HPH) is currently classified into Group 3 of the five different groups of pulmonary hypertensions, which are determined according to the cause of the disease. HPH mainly develops as a product of lung diseases, among the most prevalent causes of obstructive sleep apnea (OSA), chronic obstructive pulmonary disease (COPD), or hypobaric hypoxia due to exposure to high altitudes. Additionally, cardiometabolic risk factors converge on molecular mechanisms involving overactivation of the mammalian target of rapamycin (mTOR), which correspond to a central axis in the development of HPH. The aim of this review is to summarize the role of mTOR in the development of HPH associated with metabolic risk factors and its therapeutic alternatives, which will be discussed in this review.
肺动脉高压的病理生理学是复杂的和多因素的。它是一种以肺血管阻力持续增加为特征的疾病，这是由于肺动脉的收缩和重塑，导致平均肺动脉压升高，随后右心室肥厚，在某些情况下会导致右心衰竭。低氧性肺动脉高压（HPH）目前被归类为五种不同类型肺动脉高压中的第 3 组，这是根据疾病的原因确定的。HPH 主要是作为肺部疾病的产物发展而来的，其中最常见的原因是阻塞性睡眠呼吸暂停（OSA）、慢性阻塞性肺疾病（COPD），或由于暴露于高海拔地区而导致的低氧。此外，心脏代谢危险因素汇聚在涉及雷帕霉素靶蛋白（mTOR）过度激活的分子机制上，这对应于 HPH 发展的一个中心轴。本综述的目的是总结 mTOR 在与代谢危险因素相关的 HPH 发展中的作用及其治疗替代方案，这将在本综述中进行讨论。
