Donate Help Contact The AHA Sign In Home
American Heart Association
Circulation
Search: search_blue_button Advanced Search
Circulation. 2006;113:1857-1864
Published online before print April 10, 2006, doi: 10.1161/CIRCULATIONAHA.105.591321
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
113/15/1857    most recent
CIRCULATIONAHA.105.591321v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Eddahibi, S.
Right arrow Articles by Adnot, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Eddahibi, S.
Right arrow Articles by Adnot, S.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Medline Plus Health Information
*Pulmonary Hypertension
Related Collections
Right arrow Pulmonary circulation and disease
Right arrow Remodeling
Right arrow Smooth muscle proliferation and differentiation

(Circulation. 2006;113:1857-1864.)
© 2006 American Heart Association, Inc.


Hypertension

Cross Talk Between Endothelial and Smooth Muscle Cells in Pulmonary Hypertension

Critical Role for Serotonin-Induced Smooth Muscle Hyperplasia

Saadia Eddahibi, PhD; Christophe Guignabert, PhD; Anne-Marie Barlier-Mur, BS; Laurence Dewachter, MS; Elie Fadel, MD; Philippe Dartevelle, MD; Marc Humbert, MD; Gerald Simonneau, MD; Naïma Hanoun, MS; Françoise Saurini, MS; Michel Hamon, PhD; Serge Adnot, MD

From INSERM U651 and Département de Physiologie, Hôpital H. Mondor, AP-HP, Créteil (S.E., C.G., M.-M.B.-M., L.D., S.A.); UMR 677 INSERM/UPMC, NeuroPsychoPharmacologie, Faculté de Médecine Pitié-Salpêtrière, Paris (N.H., F.S., M.H.); Service de Pneumologie, Hôpital A. Béclère, AP-HP, Clamart (M.H., G.S.); and UPRES EA2705, Service de Chirurgie Thoracique, Vasculaire et de Transplantation Cardiopulmonaire, Hôpital Marie Lannelongue, Le Plessis Robinson (E.F., P.D.), France.

Correspondence to Saadia Eddahibi, INSERM U651, Faculté de Médecine, 8 Rue du Général Sarrail, 94010 Créteil, France. E-mail saadia.eddahibi{at}creteil.inserm.fr

Received September 28, 2005; revision received February 8, 2006; accepted February 9, 2006.

Background— The mechanism of pulmonary artery smooth muscle cell (PA-SMC) hyperplasia in idiopathic pulmonary artery hypertension (iPH) may involve both an inherent characteristic of PA-SMCs and abnormal control by external stimuli. We investigated the role of pulmonary microvascular endothelial cells (P-ECs) in controlling PA-SMC growth.

Methods and Results— Serum-free medium of quiescent P-ECs elicited marked PA-SMC proliferation, and this effect was greater with P-ECs from patients with iPH than from control subjects and greater with PA-SMCs from these patients than from control subjects. Fluoxetine, which inhibits serotonin-induced mitogenesis by blocking the serotonin transporter, and p-chlorophenylalanine, which inhibits serotonin synthesis by blocking tryptophan hydroxylase (TPH), caused a similar 60% reduction in the growth-promoting effect of P-EC media, whereas endothelin receptor blockers had no effect. Assays of TPH activity in P-EC medium based on p-chlorophenylalanine–sensitive 5-hydroxytryptophan accumulation or serotonin determination indicated serotonin synthesis by P-ECs and an increase in this TPH-dependent process in iPH. Expression of the tph1 gene encoding the peripheral form of the TPH enzyme was increased in lungs and P-ECs from patients with iPH. Lung TPH1 immunostaining was confined to the pulmonary vessel intima.

Conclusions— P-ECs produce paracrine factors governing PA-SMC growth. Serotonin, the main P-EC–derived growth factor, is overproduced in iPH and contributes to PA-SMC hyperplasia.


 

CLINICAL PERSPECTIVE




This article has been cited by other articles:


Home page
Am. J. Respir. Cell Mol. Bio.Home page
C. D. Ochoa, H. Baker, S. Hasak, R. Matyal, A. Salam, C. A. Hales, W. Hancock, and D. A. Quinn
Cyclic Stretch Affects Pulmonary Endothelial Cell Control of Pulmonary Smooth Muscle Cell Growth
Am. J. Respir. Cell Mol. Biol., July 1, 2008; 39(1): 105 - 112.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
K. M. Chin and L. J. Rubin
Pulmonary arterial hypertension.
J. Am. Coll. Cardiol., April 22, 2008; 51(16): 1527 - 1538.
[Abstract] [Full Text] [PDF]


Home page
Eur Respir JHome page
E. K. Weir, M. Obreztchikova, and Z. Hong
Fenfluramine: riddle or Rosetta stone?
Eur. Respir. J., February 1, 2008; 31(2): 232 - 235.
[Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
D. Zolkowska, M. H. Baumann, and R. B. Rothman
Chronic Fenfluramine Administration Increases Plasma Serotonin (5-Hydroxytryptamine) to Nontoxic Levels
J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 791 - 797.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Respir. Crit. Care Med.Home page
E. Fornaro, D. Li, J. Pan, and J. Belik
Prenatal Exposure to Fluoxetine Induces Fetal Pulmonary Hypertension in the Rat
Am. J. Respir. Crit. Care Med., November 15, 2007; 176(10): 1035 - 1040.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Respir. Crit. Care Med.Home page
O. Sanchez, E. Marcos, F. Perros, E. Fadel, L. Tu, M. Humbert, P. Dartevelle, G. Simonneau, S. Adnot, and S. Eddahibi
Role of Endothelium-derived CC Chemokine Ligand 2 in Idiopathic Pulmonary Arterial Hypertension
Am. J. Respir. Crit. Care Med., November 15, 2007; 176(10): 1041 - 1047.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
A. E. Linder, W. Ni, J. L. Diaz, T. Szasz, R. Burnett, and S. W. Watts
Serotonin (5-HT) in Veins: Not All in Vain
J. Pharmacol. Exp. Ther., November 1, 2007; 323(2): 415 - 421.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
M. Izikki, N. Hanoun, E. Marcos, L. Savale, A. M. Barlier-Mur, F. Saurini, S. Eddahibi, M. Hamon, and S. Adnot
Tryptophan hydroxylase 1 knockout and tryptophan hydroxylase 2 polymorphism: effects on hypoxic pulmonary hypertension in mice
Am J Physiol Lung Cell Mol Physiol, October 1, 2007; 293(4): L1045 - L1052.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
W. C. Aird
Phenotypic Heterogeneity of the Endothelium: II. Representative Vascular Beds
Circ. Res., February 2, 2007; 100(2): 174 - 190.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
I. Morecroft, Y. Dempsie, M. Bader, D. J. Walther, K. Kotnik, L. Loughlin, M. Nilsen, and M. R. MacLean
Effect of Tryptophan Hydroxylase 1 Deficiency on the Development of Hypoxia-Induced Pulmonary Hypertension
Hypertension, January 1, 2007; 49(1): 232 - 236.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Respir. Crit. Care Med.Home page
L. Dewachter, S. Adnot, E. Fadel, M. Humbert, B. Maitre, A.-M. Barlier-Mur, G. Simonneau, M. Hamon, R. Naeije, and S. Eddahibi
Angiopoietin/Tie2 Pathway Influences Smooth Muscle Hyperplasia in Idiopathic Pulmonary Hypertension
Am. J. Respir. Crit. Care Med., November 1, 2006; 174(9): 1025 - 1033.
[Abstract] [Full Text] [PDF]