Institute of Health Studies, University Arturo Prat, Av. Arturo Prat 2120, Iquique 1110939, Chile.
Institute DECIPHER, German-Chilean Institute for Research on Pulmonary Hypoxia and Its Health Sequelae, 20251 Hamburg, Germany and Iquique 1100000, Chile.
Int J Mol Sci. 2022 Jun 1;23(11):6205. doi: 10.3390/ijms23116205.
Hypoxic pulmonary hypertension (HPH) is characterized by sustained elevation of pulmonary artery pressure produced by vasoconstriction and hyperproliferative remodeling of the pulmonary artery and subsequent right ventricular hypertrophy (RVH). The search for therapeutic targets for cardiovascular pathophysiology has extended in many directions. However, studies focused on mitigating high-altitude pulmonary hypertension (HAPH) have been rare. Because AMP-activated protein kinase (AMPK) is involved in cardiovascular and metabolic pathology, AMPK is often studied as a potential therapeutic target. AMPK is best characterized as a sensor of cellular energy that can also restore cellular metabolic homeostasis. However, AMPK has been implicated in other pathways with vasculoprotective effects. Notably, cellular metabolic stress increases the intracellular ADP/ATP or AMP/ATP ratio, and AMPK activation restores ATP levels by activating energy-producing catabolic pathways and inhibiting energy-consuming anabolic pathways, such as cell growth and proliferation pathways, promoting cardiovascular protection. Thus, AMPK activation plays an important role in antiproliferative, antihypertrophic and antioxidant pathways in the pulmonary artery in HPH. However, AMPK plays contradictory roles in promoting HPH development. This review describes the main findings related to AMPK participation in HPH and its potential as a therapeutic target. It also extrapolates known AMPK functions to discuss the less-studied HAPH context.
低氧性肺动脉高压（HPH）的特征是肺动脉收缩和增生性重塑导致肺动脉压持续升高，随后出现右心室肥厚（RVH）。针对心血管病理生理学的治疗靶点的研究已经扩展到许多方向。然而，针对高原性肺动脉高压（HAPH）的研究却很少。由于 AMP 激活的蛋白激酶（AMPK）参与心血管和代谢病理学，因此 AMPK 通常被视为潜在的治疗靶点。AMPK 最显著的特征是作为细胞能量的传感器，也可以恢复细胞代谢的动态平衡。然而，AMPK 还参与了具有血管保护作用的其他途径。值得注意的是，细胞代谢应激会增加细胞内 ADP/ATP 或 AMP/ATP 的比值，AMPK 的激活通过激活产生能量的分解代谢途径和抑制消耗能量的合成代谢途径（如细胞生长和增殖途径）来恢复 ATP 水平，从而促进心血管保护。因此，AMPK 的激活在 HPH 肺动脉中的抗增殖、抗肥大和抗氧化途径中发挥重要作用。然而，AMPK 在促进 HPH 发展中发挥着矛盾的作用。这篇综述描述了与 AMPK 参与 HPH 及其作为治疗靶点的潜力相关的主要发现，并从已知的 AMPK 功能推断出较少研究的 HAPH 背景。
