Overexpression of the 5-hydroxytryptamine transporter gene - Effect on pulmonary hemodynamics and hypoxia-induced pulmonary hypertension
Overexpression of the 5-hydroxytryptamine transporter gene - Effect on pulmonary hemodynamics and hypoxia-induced pulmonary hypertension
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DOI：
10.1161/01.cir.0000127375.56172.92
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发表时间：
2004-05-04
期刊：
影响因子：
37.8
通讯作者：
Harmar, A
中科院分区：
文献类型：
--
作者：
MacLean, MR;Deuchar, GA;Harmar, A
背景-5-羟色胺(5-羟色胺，5-羟色胺)转运体活性在人类家族性肺动脉高压中被观察到。方法和结果-我们研究了5-羟色胺转运体基因高表达小鼠(5-HTT+小鼠)的肺血流动力学和缺氧性肺动脉高压和肺血管重构的发生发展。与野生型对照组相比，常氧5-HTT+组小鼠右室压升高了3倍。低氧诱导的右心室肥厚和肺血管重塑的增加在5-HTT+组小鼠中也得到加强。5-HTT+组小鼠肺内5-HTT样免疫反应、蛋白和结合部位显著增加。然而，缺氧降低了野生型和5-HTT+小鼠的5-羟色胺转运体的免疫反应性、mRNA转录、蛋白和结合部位。结论：5-羟色胺转运体的表达增加导致右室压升高，这种升高发生在右室肥厚或肺动脉重构开始之前。然而，低氧诱导的重塑在5-HTT+小鼠中增加，而低氧抑制5-HTT的表达。这提供了一个独特的模型，显示了家族性肺动脉高压和肺动脉高压伴低氧血症的不同机制。
Background - Increased serotonin (5-hydroxytryptamine, 5-HT) transporter activity has been observed in human familial pulmonary hypertension.Methods and Results - We investigated pulmonary hemodynamics and the development of hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling in mice overexpressing the gene for the 5-HT transporter (5-HTT + mice). Right ventricular pressure was elevated 3-fold in normoxic 5-HTT + mice compared with their wild-type controls. Hypoxia-induced increases in right ventricular hypertrophy and pulmonary vascular remodeling were also potentiated in the 5-HTT+ mice. 5-HTT - like immunoreactivity, protein, and binding sites were markedly increased in the lungs from the 5-HTT+ mice. Hypoxia, however, decreased 5-HT transporter immunoreactivity, mRNA transcription, protein, and binding sites in both wild-type and 5-HTT + mice.Conclusions - Increased 5-HT transporter expression causes elevated right ventricular pressures, and this occurs before the onset of right ventricular hypertrophy or pulmonary arterial remodeling. Hypoxia-induced remodeling is, however, increased in 5-HTT + mice, whereas hypoxia inhibits 5-HTT expression. This provides a unique model that demonstrates differential mechanisms for familial pulmonary arterial hypertension and pulmonary arterial hypertension with hypoxemia.