Document Detail


C-Kit Positive Cells Accumulate in Remodeled Vessels of Idiopathic Pulmonary Arterial Hypertension.
MedLine Citation:
PMID:  21471108     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
RATIONALE: c-kit positive cells, including bone marrow (BM)-derived progenitors and mast cells, may participate in vascular remodelling. As recent studies suggest that c-kit may be a target for innovative therapies in experimental pulmonary hypertension, we investigated the contribution of c-kit+ cells in human idiopathic pulmonary arterial hypertension (IPAH). Objectives and METHODS: Single c-kit, CXCL12/SDF-1α, CXCR4, CD34, and multiple c-kit, α-smooth muscle actin (α-SMA) and tryptase immunostainings were performed in IPAH lungs. C-kit mRNA expression was quantified by real-time PCR in microdissected pulmonary arteries from IPAH patients and controls. Phenotype and function of circulating progenitors were analyzed by flow cytometry. Plasma levels of soluble c-kit and CXCL12/SDF-1α were measured by ELISA. MEASUREMENTS AND MAIN RESULTS: Infiltration of c-kit+ cells in pulmonary arterial lesions was associated with an increase in c-kit mRNA expression (P<0.01 as compared to controls). Both c-kit+/tryptase+ mast cells and c-kit+/tryptase- BM-derived cells were increased in pulmonary arteries of IPAH patients, as compared to controls (106.6±54.5 versus 28±16.8/mm² and 143.8±101.1 versus 23.3±11.9/mm², all P<0.01). Plasma soluble c-kit was increased in IPAH compared to controls (27.4±12.4 vs 19.5±5.8ng/ml, P<0.05). Two populations of circulating BM-derived cells (lin-CD34highCD133high(c-kithighCXCR4low) and lin-CD34lowCD133-(c-kitlowCXCR4high)) were increased in IPAH as compared to controls (P=0.01). Pulmonary arterial lesions were associated with vasa vasorum expansion expressing CXL12/SDF-1α that may recruit c-kit+ cells. CONCLUSION: In IPAH, c-kit+ cells infiltrate pulmonary arterial lesions and may participate to vascular remodeling. Therefore, c-kit may represent a potential target for innovative PAH therapy.
Authors:
David Montani; Frédéric Perros; Natalia Gambaryan; Barbara Girerd; Peter Dorfmuller; Laura C Price; Alice Huertas; Hamida Hammad; Bart Lambrecht; Gérald Simonneau; Jean-Marie Launay; Sylvia Cohen-Kaminsky; Marc Humbert
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-4
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  -     ISSN:  1535-4970     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-4-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Faculté de Médecine, Univ. Paris-Sud, Kremlin-Bicêtre, France; Service de Pneumologie et Réanimation Respiratoire, Hôpital Antoine Béclère, Centre National de Référence de l'Hypertension Pulmonaire Sévère, Clamart, France; Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
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