Serotonin and Pulmonary Hypertension; Sex and Drugs and ROCK and Rho.
Serotonin and Pulmonary Hypertension; Sex and Drugs and ROCK and Rho.
复制标题
血清素和肺动脉高压；
DOI：
10.1002/cphy.c220004
复制
发表时间：
2022
影响因子：
5.8
通讯作者：
MacLean MR
中科院分区：
文献类型：
--
作者：
MacLean MR
血清素通常被称为“快乐激素”，因为它能保持良好的情绪、幸福感和幸福感。它参与神经细胞之间的交流，并在睡眠和消化中发挥作用。然而，过多的5 -羟色胺可能具有致病作用，肺动脉高压（PAH）患者肺动脉内皮细胞中5 -羟色胺的合成升高。PAH的特征是肺动脉压升高、右心衰、炎症和肺血管重构；血清素已被证明与这些疾病有关。机体外周血清素合成的限速酶是色氨酸羟化酶1 （TPH1）。PAH患者肺动脉内皮细胞中TPH1表达和血清素合成升高。在肺动脉内皮中合成的血清素能以旁分泌的方式作用于邻近的肺动脉平滑肌细胞（PASMCs）、内皮巨噬细胞和成纤维细胞。在人类中，血清素通过血清素转运体（SERT）进入PASMCs细胞，并与质膜上的5‐HT1B受体合作；这激活了收缩和增殖信号通路。当5 -羟色胺与减肥药如芬氟拉明、氨诺米和氯芬特明引起的多环芳烃有关时，“肺动脉高压的5 -羟色胺假说”就出现了；这些作为间接血清素能激动剂，通过SERT从血小板和细胞中释放血清素。本文就血清素在PAH中的作用作一综述。靶向5 -羟色胺合成或信号传导是一种有希望的新替代方法，可能导致PAH的新治疗方法。©2022美国生理学会。中国生物医学工程学报（英文版），2016。
Serotonin is often referred to as a “happy hormone” as it maintains good mood, well‐being, and happiness. It is involved in communication between nerve cells and plays a role in sleeping and digestion. However, too much serotonin can have pathogenic effects and serotonin synthesis is elevated in pulmonary artery endothelial cells from patients with pulmonary arterial hypertension (PAH). PAH is characterized by elevated pulmonary pressures, right ventricular failure, inflammation, and pulmonary vascular remodeling; serotonin has been shown to be associated with these pathologies. The rate‐limiting enzyme in the synthesis of serotonin in the periphery of the body is tryptophan hydroxylase 1 (TPH1). TPH1 expression and serotonin synthesis are elevated in pulmonary artery endothelial cells in patients with PAH. The serotonin synthesized in the pulmonary arterial endothelium can act on the adjacent pulmonary arterial smooth muscle cells (PASMCs), adventitial macrophages, and fibroblasts, in a paracrine fashion. In humans, serotonin enters PASMCs cells via the serotonin transporter (SERT) and it can cooperate with the 5‐HT1B receptor on the plasma membrane; this activates both contractile and proliferative signaling pathways. The “serotonin hypothesis of pulmonary hypertension” arose when serotonin was associated with PAH induced by diet pills such as fenfluramine, aminorex, and chlorphentermine; these act as indirect serotonergic agonists causing the release of serotonin from platelets and cells through the SERT. Here the role of serotonin in PAH is reviewed. Targeting serotonin synthesis or signaling is a promising novel alternative approach which may lead to novel therapies for PAH. © 2022 American Physiological Society.Compr Physiol12: 4103–4118, 2022.