Advertisement

Citations to this article

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

×

Total citations by year

Year: 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 Total
Citations: 7 4 12 10 11 17 13 10 6 9 6 5 3 2 115
Citation information

Citations to this article in year 2008 (13)

Title and authors Publication Year
The role of gene polymorphisms in the pathogenesis of chronic obstructive pulmonary disease
E Slabá, P Joppa, J Šalagovič, R Tkáčová
Biologia 2008
Pulmonary hypertension associated with COPD
J Elwing, RJ Panos
International journal of chronic obstructive pulmonary disease 2008
Pathogenic mechanisms of pulmonary arterial hypertension
SY Chan, J Loscalzo
Journal of Molecular and Cellular Cardiology 2008
How the serotonin story is being rewritten by new gene-based discoveries principally related to SLC6A4, the serotonin transporter gene, which functions to influence all cellular serotonin systems
DL Murphy, MA Fox, KR Timpano, PR Moya, R Ren-Patterson, AM Andrews, A Holmes, KP Lesch, JR Wendland
Neuropharmacology 2008
Novel interactions between the 5-HT transporter, 5-HT1B receptors and Rho kinase in vivo and in pulmonary fibroblasts
KM Mair, MR MacLean, I Morecroft, Y Dempsie, TM Palmer
British Journal of Pharmacology 2008
Pulmonary hypertension: therapeutic targets within the serotonin system
Y Dempsie, MR MacLean
British Journal of Pharmacology 2008
Valvular regurgitation and surgery associated with fenfluramine use: an analysis of 5743 individuals
CF Dahl, MR Allen, PM Urie, PN Hopkins
BMC Medicine 2008
Dual dopamine/serotonin releasers: potential treatment agents for stimulant addiction
RB Rothman, BE Blough, MH Baumann
Experimental and Clinical Psychopharmacology 2008
Analysis of a functional serotonin transporter promoter polymorphism in psoriasis vulgaris
R Mössner, G Stiens, IR König, D Schmidt, A Platzer, U Krüger, K Reich
Archives of Dermatological Research 2008
Phospholipase D signaling in serotonin-induced mitogenesis of pulmonary artery smooth muscle cells
Y Liu, BL Fanburg
American journal of physiology. Lung cellular and molecular physiology 2008
Evidence of a role for osteoprotegerin in the pathogenesis of pulmonary arterial hypertension
A Lawrie, E Waterman, M Southwood, D Evans, J Suntharalingam, S Francis, D Crossman, P Croucher, N Morrell, C Newman
The American Journal of Pathology 2008
Medical therapy for pulmonary arterial hypertension
JA Driscoll, MM Chakinala
Expert Opinion on Pharmacotherapy 2008
Role of the serotonin transporter in pulmonary arterial hypertension
Y Dempsie, MR MacLean
Expert Review of Clinical Pharmacology 2008

Advertisement
Advertisement