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Abstract

Hyperplasia of pulmonary artery smooth muscle cells (PA-SMCs) is a hallmark pathological feature of primary pulmonary hypertension (PPH). Here we found that PA-SMCs from patients with PPH grow faster than PA-SMCs from controls when stimulated by serotonin or serum and that these effects are due to increased expression of the serotonin transporter (5-HTT), which mediates internalization of indoleamine. In the presence of 5-HTT inhibitors, the growth stimulatory effects of serum and serotonin were markedly reduced and the difference between growth of PA-SMCs from patients and controls was no longer observed. As compared with controls, the expression of 5-HTT was increased in cultured PA-SMCs as well as in platelets and lungs from patients with PPH where it predominated in the media of thickened pulmonary arteries and in onion-bulb lesions. The L-allelic variant of the 5HTT gene promoter, which is associated with 5-HTT overexpression and increased PA-SMC growth, was present in homozygous form in 65% of patients but in only 27% of controls. We conclude that 5-HTT activity plays a key role in the pathogenesis of PA-SMC proliferation in PPH and that a 5HTT polymorphism confers susceptibility to PPH.

Authors

Saadia Eddahibi ... Michel Hamon, Serge Adnot

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Year: 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 Total
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Citations to this article in year 2006 (6)

Title and authors Publication Year
Upregulated genes in sporadic, idiopathic pulmonary arterial hypertension
AJ Edgar, MR Chacón, AE Bishop, MH Yacoub, JM Polak
Respiratory Research 2006
Serotonin induces pulmonary artery smooth muscle cell migration
RM Day, AS Agyeman, MJ Segel, RD Chévere, JM Angelosanto, YJ Suzuki, BL Fanburg
Biochemical Pharmacology 2006
SERTRALINE PROTECTS AGAINST MONOCROTALINE-INDUCED PULMONARY HYPERTENSION IN RATS
XQ Li, Y Hong, Y Wang, XH Zhang, HL Wang
Clinical and Experimental Pharmacology and Physiology 2006
Pulmonary arterial hypertension: New insights and new hope
KB MARTIN, JR KLINGER, SI ROUNDS
Respirology 2006
Pulmonary arterial hypertension
A Raiesdana, J Loscalzo
Annals of Medicine 2006
Of Minds and Embryos: Left-Right Asymmetry and the Serotonergic Controls of Pre-Neural Morphogenesis
M Levin, GA Buznikov, JM Lauder
Developmental Neuroscience 2006

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