Zhao Qiang, Song Ping, Zou Ming-Hui
Center for Molecular and Translational Medicine, Georgia State University, Atlanta, GA, United States.
Front Cell Dev Biol. 2021 Jun 8;9:691585. doi: 10.3389/fcell.2021.691585. eCollection 2021.
Pulmonary hypertension (PH) is a debilitating and life-threatening disease characterized by increased blood pressure within the pulmonary arteries. Adenosine monophosphate-activated protein kinase (AMPK) is a heterotrimeric serine-threonine kinase that contributes to the regulation of metabolic and redox signaling pathways. It has key roles in the regulation of cell survival and proliferation. The role of AMPK in PH is controversial because both inhibition and activation of AMPK are preventive against PH development. Some clinical studies found that metformin, the first-line antidiabetic drug and the canonical AMPK activator, has therapeutic efficacy during treatment of early-stage PH. Other study findings suggest the use of metformin is preferentially beneficial for treatment of PH associated with heart failure with preserved ejection fraction (PH-HFpEF). In this review, we discuss the "AMPK paradox" and highlight the differential effects of AMPK on pulmonary vasoconstriction and pulmonary vascular remodeling. We also review the effects of AMPK activators and inhibitors on rescue of preexisting PH in animals and include a discussion of gender differences in the response to metformin in PH.
肺动脉高压（PH）是一种使人虚弱且危及生命的疾病，其特征是肺动脉内血压升高。单磷酸腺苷激活蛋白激酶（AMPK）是一种异源三聚体丝氨酸 - 苏氨酸激酶，有助于调节代谢和氧化还原信号通路。它在细胞存活和增殖的调节中起关键作用。AMPK在PH中的作用存在争议，因为抑制和激活AMPK都可预防PH的发展。一些临床研究发现，一线抗糖尿病药物二甲双胍作为典型的AMPK激活剂，在早期PH治疗中具有治疗效果。其他研究结果表明，二甲双胍优先有利于治疗与射血分数保留的心力衰竭相关的肺动脉高压（PH-HFpEF）。在这篇综述中，我们讨论了“AMPK悖论”，并强调了AMPK对肺血管收缩和肺血管重塑的不同影响。我们还回顾了AMPK激活剂和抑制剂对挽救动物已有的PH的作用，并讨论了PH患者对二甲双胍反应中的性别差异。
