Converging evidence in support of the serotonin hypothesis of dexfenfluramine-induced pulmonary hypertension with novel transgenic mice

Yvonne Dempsie, Ian Morecroft, David Welsh, Neil MacRitchie, Lynn Loughlin, Margaret Nilsen, Andrew Peacock, Anthony Harmar, Michael Bader, Margaret R. MacLean

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Abstract

The incidence of pulmonary arterial hypertension secondary to the use of indirect serotinergic agonists such as aminorex and dexfenfluramine led to the “serotonin hypothesis” of pulmonary arterial hypertension; however, the role of serotonin in dexfenfluramine-induced pulmonary arterial hypertension remains controversial. Here, we used novel transgenic mice lacking peripheral serotonin (deficient in tryptophan hydroxylase-1; Tph1-/- mice) or overexpressing the gene for the human serotonin transporter (SERT; SERT+ mice) to investigate this further.
Original languageEnglish
Pages (from-to)2928-2937
Number of pages10
JournalCirculation
Volume117
Issue number22
DOIs
Publication statusPublished - Jun 2008

Keywords

  • pulmonary arterial hypertension
  • PAH
  • serotinergic agonists
  • serotonin
  • gene expression

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    Dempsie, Y., Morecroft, I., Welsh, D., MacRitchie, N., Loughlin, L., Nilsen, M., Peacock, A., Harmar, A., Bader, M., & MacLean, M. R. (2008). Converging evidence in support of the serotonin hypothesis of dexfenfluramine-induced pulmonary hypertension with novel transgenic mice. Circulation, 117(22), 2928-2937 . https://doi.org/10.1161/CIRCULATIONAHA.108.767558