Overexpression of the 5-hydroxytryptamine transporter gene effect on pulmonary hemodynamics and hypoxia-Induced pulmonary hypertension

Margaret R. MacLean, Graeme A. Deuchar, Martin N. Hicks, Ian Morecroft, Sanbeg Shen, John Sheward, Janet Colston, Lynn Loughlin, Margaret Nilsen, Yvonne Dempsie, Anthony Harmar

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
Pages (from-to)2150-5
Number of pages6
JournalCirculation
Volume109
Issue number17
DOIs
Publication statusPublished - 3 May 2004

Keywords

  • hypoxia
  • pulmonary hypertension
  • serotonin
  • remodelling

Fingerprint Dive into the research topics of 'Overexpression of the 5-hydroxytryptamine transporter gene effect on pulmonary hemodynamics and hypoxia-Induced pulmonary hypertension'. Together they form a unique fingerprint.

  • Cite this

    MacLean, M. R., Deuchar, G. A., Hicks, M. N., Morecroft, I., Shen, S., Sheward, J., Colston, J., Loughlin, L., Nilsen, M., Dempsie, Y., & Harmar, A. (2004). Overexpression of the 5-hydroxytryptamine transporter gene effect on pulmonary hemodynamics and hypoxia-Induced pulmonary hypertension. Circulation, 109(17), 2150-5. https://doi.org/10.1161/01.CIR.0000127375.56172.92