Section of Cardiology, Department of Medicine, University of Chicago, 5841 South Maryland Avenue, MC6080, Chicago, IL, 60637, USA.
Adv Exp Med Biol. 2010;661:171-85. doi: 10.1007/978-1-60761-500-2_11.
Pulmonary arterial hypertension (PAH) is a disease of the pulmonary vasculature that is characterized by vascular obstruction and progressive right ventricular failure. One hallmark of clinical PAH is its very poor survival, with PAH mortality rates approximating those of many malignancies. The discovery that the fawn-hooded rat strain (FHR) spontaneously develops PAH has allowed for major insights into the pathophysiology of PAH. These findings have revealed that cancer and PAH not only share a similarly poor prognosis but also demonstrate similar resistance to apoptosis and activation of cell proliferation as a major pathophysiologic mechanism. One of the causes for the resistance to apoptosis and increased proliferation of pulmonary vascular smooth muscle cells in PAH is a cancer-like metabolic shift towards a glycolytic metabolism (Warburg effect) and down-regulation of mitochondrial glucose oxidation. This book chapter will review the role of such a metabolic shift in the pathophysiology of PAH and also highlight emerging anti-proliferative PAH therapies that correct the metabolic dysregulation in PAH.
肺动脉高压（PAH）是一种肺血管疾病，其特征为血管阻塞和进行性右心室衰竭。临床 PAH 的一个显著特征是其极差的生存率，PAH 的死亡率与许多恶性肿瘤相当。法恩霍德大鼠（FHR）自发发生 PAH 的发现，使人们对 PAH 的病理生理学有了重大的了解。这些发现表明，癌症和 PAH 不仅具有相似的预后不良，而且还表现出对细胞凋亡和细胞增殖激活的类似抵抗，这是主要的病理生理机制。PAH 中肺血管平滑肌细胞对细胞凋亡的抵抗和增殖增加的原因之一是类似癌症的代谢向糖酵解代谢（Warburg 效应）转变，以及线粒体葡萄糖氧化的下调。本章将回顾这种代谢转变在 PAH 病理生理学中的作用，并强调新兴的抗增殖性 PAH 疗法，这些疗法可纠正 PAH 中的代谢失调。
