Prasad Kailash
Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Int J Angiol. 2019 Jun;28(2):71-79. doi: 10.1055/s-0039-1687818. Epub 2019 Apr 19.
Pulmonary hypertension (PH) is a rare and fatal disease characterized by elevation of pulmonary artery pressure ≥ 25 mm Hg. There are five groups of PH: (1) pulmonary artery (PA) hypertension (PAH), (2) PH due to heart diseases, (3) PH associated with lung diseases/hypoxia, (4) PH associated with chronic obstruction of PA, and (5) PH due to unclear and/or multifactorial mechanisms. The pathophysiologic mechanisms of group 1 have been studied in detail; however, those for groups 2 to 5 are not that well known. PH pathology is characterized by smooth muscle cells (SMC) proliferation, muscularization of peripheral PA, accumulation of extracellular matrix (ECM), plexiform lesions, thromboembolism, and recanalization of thrombi. Advanced glycation end products (AGE) and its receptor (RAGE) and soluble RAGE (sRAGE) appear to be involved in the pathogenesis of PH. AGE and its interaction with RAGE induce vascular hypertrophy through proliferation of vascular SMC, accumulation of ECM, and suppression of apoptosis. Reactive oxygen species (ROS) generated by interaction of AGE and RAGE modulates SMC proliferation, attenuate apoptosis, and constricts PA. Increased stiffness in the artery due to vascular hypertrophy, and vasoconstriction due to ROS resulted in PH. The data also suggest that reduction in consumption and formation of AGE, suppression of RAGE expression, blockage of RAGE ligand binding, elevation of sRAGE levels, and antioxidants may be novel therapeutic targets for prevention, regression, and slowing of progression of PH. In conclusion, AGE-RAGE stress may be involved in the pathogenesis of PH and the therapeutic targets should be the AGE-RAGE axis.
肺动脉高压（PH）是一种罕见的致命疾病，其特征为肺动脉压力升高≥25 mmHg。PH分为五组：（1）肺动脉（PA）高压（PAH），（2）心脏病所致PH，（3）与肺部疾病/缺氧相关的PH，（4）与PA慢性阻塞相关的PH，以及（5）病因不明和/或多因素机制所致的PH。第1组的病理生理机制已得到详细研究；然而，第2至5组的机制尚不太清楚。PH的病理学特征为平滑肌细胞（SMC）增殖、外周PA肌化、细胞外基质（ECM）积聚、丛状病变、血栓栓塞以及血栓再通。晚期糖基化终末产物（AGE）及其受体（RAGE）和可溶性RAGE（sRAGE）似乎参与了PH的发病机制。AGE及其与RAGE的相互作用通过血管SMC增殖、ECM积聚和细胞凋亡抑制诱导血管肥大。AGE与RAGE相互作用产生的活性氧（ROS）调节SMC增殖、减弱细胞凋亡并使PA收缩。血管肥大导致动脉僵硬度增加，以及ROS引起的血管收缩导致了PH。数据还表明，减少AGE的消耗和形成、抑制RAGE表达、阻断RAGE配体结合、提高sRAGE水平以及使用抗氧化剂可能是预防、逆转和减缓PH进展的新型治疗靶点。总之，AGE-RAGE应激可能参与了PH的发病机制，治疗靶点应为AGE-RAGE轴。
