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

David Montani, Frédéric Perros, Natalia Gambaryan, Barbara Girerd, Peter Dorfmuller, Laura C Price, Alice Huertas, Hamida Hammad UGent, Bart Lambrecht UGent, Gérald Simonneau, et al. (2011) AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE. 184(1). p.116-123
abstract
Rationale: 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). Objectives: To investigate the contribution of c-kit(+) cells in human IPAH. Methods: Single c-kit, CXCL12/SDF-1 alpha, CXCR4, CD34, and multiple c-kit, a-smooth muscle actin (alpha-SMA) and tryptase immunostainings were performed in IPAH lungs. C-kit mRNA expression was quantified by real-time polymerase chain reaction in microdisected 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-1 alpha 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 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 < 0.01). Plasma-soluble c-kit was increased in IPAH compared with control subjects (27.4 +/- 12.4 vs. 19.5 +/- 5.8 ng/ml; P < 0.05). Two populations of circulating BM-derived cells (lin-CD34(high)CD133(high) [c-kit(high)CXCR4(low)] and lin-CD34(low)CD133(-) [c-kit(low)CXCR4(high)]) were increased in IPAH compared with control subjects (P = 0.01). Pulmonary arterial lesions were associated with vasa vasorum expansion expressing CXL12/SDF-1 alpha that may recruit c-kit(+) cells. Conclusions: 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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
c-kit, Bone marrow-derived cells, mast cells, pulmonary arterial hypertension, stromal-derived factor-1 (CXL12/SDF-1 alpha), ENDOTHELIAL PROGENITOR CELLS, RECEPTOR TYROSINE KINASE, MAST-CELLS, NEOINTIMAL FORMATION, VOLUME OVERLOAD, HYPOXIA, EXPRESSION, INHIBITION, IMATINIB, CHYMASE
journal title
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Am. J. Respir. Crit. Care Med.
volume
184
issue
1
pages
116 - 123
Web of Science type
Article
Web of Science id
000292766700018
JCR category
RESPIRATORY SYSTEM
JCR impact factor
11.08 (2011)
JCR rank
1/48 (2011)
JCR quartile
1 (2011)
ISSN
1073-449X
DOI
10.1164/rccm.201006-0905OC
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2002847
handle
http://hdl.handle.net/1854/LU-2002847
date created
2012-01-25 12:11:12
date last changed
2016-12-19 15:39:42
@article{2002847,
  abstract     = {Rationale: 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).
Objectives: To investigate the contribution of c-kit(+) cells in human IPAH.
Methods: Single c-kit, CXCL12/SDF-1 alpha, CXCR4, CD34, and multiple c-kit, a-smooth muscle actin (alpha-SMA) and tryptase immunostainings were performed in IPAH lungs. C-kit mRNA expression was quantified by real-time polymerase chain reaction in microdisected 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-1 alpha 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 {\textlangle} 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 {\textlangle} 0.01). Plasma-soluble c-kit was increased in IPAH compared with control subjects (27.4 +/- 12.4 vs. 19.5 +/- 5.8 ng/ml; P {\textlangle} 0.05). Two populations of circulating BM-derived cells (lin-CD34(high)CD133(high) [c-kit(high)CXCR4(low)] and lin-CD34(low)CD133(-) [c-kit(low)CXCR4(high)]) were increased in IPAH compared with control subjects (P = 0.01). Pulmonary arterial lesions were associated with vasa vasorum expansion expressing CXL12/SDF-1 alpha that may recruit c-kit(+) cells.
Conclusions: 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.},
  author       = {Montani, David and Perros, Fr{\'e}d{\'e}ric and Gambaryan, Natalia and Girerd, Barbara and Dorfmuller, Peter and Price, Laura C and Huertas, Alice and Hammad, Hamida and Lambrecht, Bart and Simonneau, G{\'e}rald and Launay, Jean-Marie and Cohen-Kaminsky, Sylvia and Humbert, Marc},
  issn         = {1073-449X},
  journal      = {AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE},
  keyword      = {c-kit,Bone marrow-derived cells,mast cells,pulmonary arterial hypertension,stromal-derived factor-1 (CXL12/SDF-1 alpha),ENDOTHELIAL PROGENITOR CELLS,RECEPTOR TYROSINE KINASE,MAST-CELLS,NEOINTIMAL FORMATION,VOLUME OVERLOAD,HYPOXIA,EXPRESSION,INHIBITION,IMATINIB,CHYMASE},
  language     = {eng},
  number       = {1},
  pages        = {116--123},
  title        = {C-Kit-positive cells accumulate in remodeled vessels of idiopathic pulmonary arterial hypertension},
  url          = {http://dx.doi.org/10.1164/rccm.201006-0905OC},
  volume       = {184},
  year         = {2011},
}

Chicago
Montani, David, Frédéric Perros, Natalia Gambaryan, Barbara Girerd, Peter Dorfmuller, Laura C Price, Alice Huertas, et al. 2011. “C-Kit-positive Cells Accumulate in Remodeled Vessels of Idiopathic Pulmonary Arterial Hypertension.” American Journal of Respiratory and Critical Care Medicine 184 (1): 116–123.
APA
Montani, D., Perros, F., Gambaryan, N., Girerd, B., Dorfmuller, P., Price, L. C., Huertas, A., et al. (2011). C-Kit-positive cells accumulate in remodeled vessels of idiopathic pulmonary arterial hypertension. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 184(1), 116–123.
Vancouver
1.
Montani D, Perros F, Gambaryan N, Girerd B, Dorfmuller P, Price LC, et al. C-Kit-positive cells accumulate in remodeled vessels of idiopathic pulmonary arterial hypertension. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE. 2011;184(1):116–23.
MLA
Montani, David, Frédéric Perros, Natalia Gambaryan, et al. “C-Kit-positive Cells Accumulate in Remodeled Vessels of Idiopathic Pulmonary Arterial Hypertension.” AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 184.1 (2011): 116–123. Print.