The serotonin hypothesis in pulmonary hypertension revisited: targets for novel therapies (2017 Grover Conference Series).
The serotonin hypothesis in pulmonary hypertension revisited: targets for novel therapies (2017 Grover Conference Series).
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DOI：
10.1177/2045894018759125
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发表时间：
2018-04
影响因子：
2.6
通讯作者：
MacLean MMR
中科院分区：
文献类型：
--
作者：
MacLean MMR
肺动脉中血清素合成和/或活性的增加与肺动脉高压（PAH）的病理生物学有关。多环芳烃的发病率与减肥药如氨氟乐、芬氟拉明和氯芬特有关，最初导致了“肺动脉高压的血清素假说”。在过去的几十年里，越来越多的令人信服的证据表明，靶向5 -羟色胺合成或信号传导是开发PAH新疗法的一种新颖而有前途的方法。在PAH患者中，通过色氨酸羟化酶1 （TPH1）合成的肺内皮5-羟色胺增加，5-羟色胺可以旁分泌方式作用于肺动脉平滑肌细胞（PASMCs）。在人类中，5-羟色胺可以通过血清素转运体（SERT）进入PASMCs或激活5-HT1B受体；5-HT1B激活和SERT活性通过激活下游增殖和收缩信号通路共同诱导PASMC收缩和增殖。在这里，我们将回顾血清素假说的现状，并讨论潜在的和新的治疗靶点。
Increased synthesis of serotonin and/or activity of serotonin in pulmonary arteries has been implicated in the pathobiology of pulmonary arterial hypertension (PAH). The incidence of PAH associated with diet pills such as aminorex, fenfluramine, and chlorphentermine initially led to the “serotonin hypothesis of pulmonary hypertension.” Over the last couple of decades there has been an accumulation of convincing evidence that targeting serotonin synthesis or signaling is a novel and promising approach to the development of novel therapies for PAH. Pulmonary endothelial serotonin synthesis via tryptophan hydroxlase 1 (TPH1) is increased in patients with PAH and serotonin can act in a paracrine fashion on underlying pulmonary arterial smooth muscle cells (PASMCs), In humans, serotonin can enter PASMCs via the serotonin transporter (SERT) or activate the 5-HT1B receptor; 5-HT1B activation and SERT activity cooperate to induce PASMC contraction and proliferation via activation of downstream proliferative and contractile signaling pathways. Here we will review the current status of the serotonin hypothesis and discuss potential and novel therapeutic targets.
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影响因子：
6.2
作者：
Fox, Benjamin D.;Azoulay, Laurent;Suissa, Samy
通讯作者：
Suissa, Samy
影响因子：
--
作者：
ASHMORE, RC;RODMAN, DM;STELZNER, TJ
通讯作者：
STELZNER, TJ
影响因子：
3.3
作者：
Belohlávková, S;Simák, J;Hampl, V
通讯作者：
Hampl, V
影响因子：
4.3
作者：
Chen, Chunyan;Han, Xinyuan;Tian, Hongyan
通讯作者：
Tian, Hongyan
DOI：
10.1124/jpet.116.237933
发表时间：
2017-02-01
影响因子：
3.5
作者：
Aiello, Robert J.;Bourassa, Patricia-Ann;Paralkar, Vishwas
通讯作者：
Paralkar, Vishwas