C-kit-positive cells accumulate in remodeled vessels of idiopathic pulmonary arterial hypertension

• Published in: American journal of respiratory and critical care medicine 2011-07, Vol.184 (1), p.116-123
• Main Authors: Montani, David, Perros, Frédéric, Gambaryan, Natalia, Girerd, Barbara, Dorfmuller, Peter, Price, Laura C, Huertas, Alice, Hammad, Hamida, Lambrecht, Bart, Simonneau, Gérald, Launay, Jean-Marie, Cohen-Kaminsky, Sylvia, Humbert, Marc
• Format: Article
• Language: English
• Subjects: Antigens, CD34 - metabolism; Bone marrow; Chemokine CXCL12 - metabolism; Cloning; Connective Tissue - metabolism; Flow Cytometry; Humans; Hypertension, Pulmonary - metabolism; Hypertension, Pulmonary - pathology; Hypertension, Pulmonary - physiopathology; Immunohistochemistry; Lungs; Mast Cells - metabolism; Mast Cells - pathology; Proto-Oncogene Proteins c-kit - metabolism; Pulmonary arteries; Pulmonary Artery - metabolism; Pulmonary Artery - pathology; Pulmonary Artery - physiopathology; Pulmonary hypertension; Receptors, CXCR4 - metabolism; Smooth muscle; Stem Cells - metabolism; Stem Cells - pathology; Tryptases - metabolism; Vasa Vasorum - metabolism; Veins & arteries
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.201006-0905OC

C-kit(+) cells, including bone marrow (BM)-derived progenitors and mast cells, may participate in vascular remodelling. Because 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). To investigate the contribution of c-kit(+) cells in human IPAH. 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 polymerase chain reaction in microdissected pulmonary arteries from patients with IPAH and control subjects. 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. Infiltration of c-kit(+) cells in pulmonary arterial lesions was associated with an increase in c-kit mRNA expression (P < 0.01 compared with control subjects). Both c-kit(+)/tryptase(+) mast cells and c-kit(+)/tryptase(-) BM-derived cells were increased in pulmonary arteries of patients with IPAH compared with control subjects (106.6 ± 54.5 vs. 28 ± 16.8/mm(2) and 143.8 ± 101.1 vs. 23.3 ± 11.9/mm(2); all P