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Current Topics in Pharmacology
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Volume 14
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Crosstalk between 5-HTT and BMPR-II in development of pulmonary arterial hypertension
Wang Yun, Zhang Xin-hua, Liu Jin-rong, Wang Han-ming, Liu Ming, Han Dan-dan, Zhang Hong-yan, Zhou Fu-bo, Wang Huai-Liang
Pages: 109 - 113
Number of pages: 5
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Current Topics in Pharmacology Volume 14
Copyright © 2010 Research Trends. All rights reserved
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The mitogenic actions of serotonin (5-hydroxytryptamine, 5-HT) are transduced via the serotonin transporter (5-HTT) pathway. Progression of pulmonary hypertension is associated with increased lung expression of 5-HTT, which leads to hyperplasia of pulmonary arterial smooth muscle cells. Bone morphogenetic protein receptor type II (BMPR-II) may contribute to the maintenance of normal pulmonary vascular structure and function. Mutations in BMPR-II are now considered to be the genetic basis for familial and idiopathic pulmonary hypertension. BMPR-II mutation could allow for a heightened response to 5-HT, particularly in patients with a polymorphism allowing for heightened expression of the 5-HTT. Increased 5-HTT expression and decreased BMPR-II expression were found in monocrotaline (MCT) - induced pulmonary hypertensive rats. Selective serotonin re-uptake inhibitors (SSRIs) inhibited 5-HTT expression and reversed BMPR-II expression, accompanied by suppressing proliferation and enhancing apoptosis of pulmonary arterial smooth muscle cells (PASMCs). Therefore, altered genetic control of 5-HTT and BMPR-II may play considerable roles in pathogenesis of the vascular lesion characteristic of pulmonary hypertension, and the crosstalk between 5-HTT and BMPR-II might be closely related with the development of pulmonary arterial hypertension.
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