| C-Kit Positive Cells Accumulate in Remodeled Vessels of Idiopathic Pulmonary Arterial Hypertension. | |
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MedLine Citation:
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PMID: 21471108 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2011-2-4 |
Journal Detail:
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Title: American journal of respiratory and critical care medicine Volume: - ISSN: 1535-4970 ISO Abbreviation: - Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-4-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421642 Medline TA: Am J Respir Crit Care Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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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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