Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, Georgia.
Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia.
Adv Exp Med Biol. 2021;1303:13-32. doi: 10.1007/978-3-030-63046-1_2.
Pulmonary Arterial Hypertension (PAH) is a progressive vascular disease arising from the narrowing of pulmonary arteries (PA) resulting in high pulmonary arterial blood pressure and ultimately right ventricular (RV) failure. A defining characteristic of PAH is the excessive remodeling of PA that includes increased proliferation, inflammation, and fibrosis. There is no cure for PAH nor interventions that effectively impede or reverse PA remodeling, and research over the past several decades has sought to identify novel molecular mechanisms of therapeutic benefit. Galectin-3 (Gal-3; Mac-2) is a carbohydrate-binding lectin that is remarkable for its chimeric structure, comprised of an N-terminal oligomerization domain and a C-terminal carbohydrate-recognition domain. Gal-3 is a regulator of changes in cell behavior that contribute to aberrant PA remodeling including cell proliferation, inflammation, and fibrosis, but its role in PAH is poorly understood. Herein, we summarize the recent literature on the role of Gal-3 in the development of PAH and provide experimental evidence supporting the ability of Gal-3 to influence reactive oxygen species (ROS) production, NOX enzyme expression, inflammation, and fibrosis, which contributes to PA remodeling. Finally, we address the clinical significance of Gal-3 as a target in the development of therapeutic agents as a treatment for PAH.
肺高血压（PAH）是一种进行性血管疾病，由肺动脉（PA）狭窄引起，导致肺动脉血压升高，最终导致右心室（RV）衰竭。PAH 的一个定义特征是 PA 的过度重塑，包括增殖、炎症和纤维化增加。目前尚无治疗 PAH 的方法，也没有能够有效阻止或逆转 PA 重塑的干预措施，过去几十年的研究一直在寻找有治疗益处的新分子机制。半乳糖凝集素-3（Gal-3；Mac-2）是一种糖结合凝集素，其嵌合结构引人注目，由 N 端寡聚化结构域和 C 端糖识别结构域组成。Gal-3 是细胞行为变化的调节剂，这些变化导致异常的 PA 重塑，包括细胞增殖、炎症和纤维化，但它在 PAH 中的作用尚未被充分了解。本文总结了 Gal-3 在 PAH 发展中的作用的最新文献，并提供了支持 Gal-3 影响活性氧（ROS）产生、NOX 酶表达、炎症和纤维化，从而导致 PA 重塑的实验证据。最后，我们讨论了 Gal-3 作为治疗 PAH 的治疗剂开发中的靶标的临床意义。
