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Chemerin Alone or Added to Endothelin-1 Stimulates Rat Pulmonary Vascular Smooth Muscle Cells Proliferation, Migration and Resistance to Apoptosis
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A7680 - Chemerin Alone or Added to Endothelin-1 Stimulates Rat Pulmonary Vascular Smooth Muscle Cells Proliferation, Migration and Resistance to Apoptosis
Author Block: A. Hanthazi1, P. Jespers1, G. Vegh1, C. Dubois2, J. Springael2, L. Dewachter1, K. Mc Entee1; 1Faculté de Médecine - Laboratoire de Physiologie et Pharmacologie, Université libre de Bruxelles, Bruxelles, Belgium, 2IRIBHM, Université libre de Bruxelles, Bruxelles, Belgium.
Background:
Proliferation, resistance to apoptosis and migration of pulmonary artery smooth muscle cells (PASMCs) are characteristic pathogeneses of vascular remodeling in pulmonary arterial hypertension (PAH). Leptin and adiponectin have shown respectively deleterious and protective effects in animal models of PAH. Chemerin has been recently associated with atherosclerosis, essential hypertension and obesity-induced hypertension but its actions on the pulmonary circulation are unknown. We hypothesized that chemerin alone and/or added to endothelin-1 (ET-1), a major mediator of PAH, induce proliferation, migration and resistance to apoptosis of rat PASMCs by taking as a comparator aortic SMCs.
Methods:
Primary cultures of rat PASMCs and aortic SMCs were performed by the explant technique. Cells were used between passage 3 and 6. Proliferation was tested by bromodeoxyuridine incorporation and migration by the Transwell migration assay, both after 24-hour incubation with increasing concentrations of chemerin (from 0.5.10-8 to 10-7M) with or without ET-1 (10-7M). Fetal calf serum and serum free medium were used as positive and negative controls. Apoptosis was induced by staurosporine and quantified by detection of Annexin V/ propidium iodide-positive cells using flow cytometry after 24-hour incubation with increasing concentrations of chemerin (from 0.5.10-8 to 10-7M).
Results:
The chemerin receptor ChemR23, was widely expressed in the media of rat pulmonary arteries and in cultured PASMCs. Chemerin (from 10-8M) added to ET-1 induced PASMCs proliferation while no response was observed in aortic SMCs. Chemerin alone (from 0.5.10-8M) increased PASMCs and aortic SMCs migration. This effect was more pronounced in aortic SMCs than in PASMCS, inversely related to chemerin dose and potentiated by ET-1 addition. Chemerin induced a concentration-dependent resistance to apoptosis in PASMCs, but not in aortic SMCs.
Conclusion:
By using primary cultures of rat PASMCs and aortic SMCs, we demonstrated that chemerin alone and/or in association with ET-1 induced cellular proliferation and migration and led to resistance to apoptosis. The proliferative and apoptostic responses were PASMCs specific. These in vitro results suggest that chemerin could participate to in vivo pulmonary vascular remodeling, particularly in conditions where ET-1 is upregulated.
Author Block: A. Hanthazi1, P. Jespers1, G. Vegh1, C. Dubois2, J. Springael2, L. Dewachter1, K. Mc Entee1; 1Faculté de Médecine - Laboratoire de Physiologie et Pharmacologie, Université libre de Bruxelles, Bruxelles, Belgium, 2IRIBHM, Université libre de Bruxelles, Bruxelles, Belgium.
Background:
Proliferation, resistance to apoptosis and migration of pulmonary artery smooth muscle cells (PASMCs) are characteristic pathogeneses of vascular remodeling in pulmonary arterial hypertension (PAH). Leptin and adiponectin have shown respectively deleterious and protective effects in animal models of PAH. Chemerin has been recently associated with atherosclerosis, essential hypertension and obesity-induced hypertension but its actions on the pulmonary circulation are unknown. We hypothesized that chemerin alone and/or added to endothelin-1 (ET-1), a major mediator of PAH, induce proliferation, migration and resistance to apoptosis of rat PASMCs by taking as a comparator aortic SMCs.
Methods:
Primary cultures of rat PASMCs and aortic SMCs were performed by the explant technique. Cells were used between passage 3 and 6. Proliferation was tested by bromodeoxyuridine incorporation and migration by the Transwell migration assay, both after 24-hour incubation with increasing concentrations of chemerin (from 0.5.10-8 to 10-7M) with or without ET-1 (10-7M). Fetal calf serum and serum free medium were used as positive and negative controls. Apoptosis was induced by staurosporine and quantified by detection of Annexin V/ propidium iodide-positive cells using flow cytometry after 24-hour incubation with increasing concentrations of chemerin (from 0.5.10-8 to 10-7M).
Results:
The chemerin receptor ChemR23, was widely expressed in the media of rat pulmonary arteries and in cultured PASMCs. Chemerin (from 10-8M) added to ET-1 induced PASMCs proliferation while no response was observed in aortic SMCs. Chemerin alone (from 0.5.10-8M) increased PASMCs and aortic SMCs migration. This effect was more pronounced in aortic SMCs than in PASMCS, inversely related to chemerin dose and potentiated by ET-1 addition. Chemerin induced a concentration-dependent resistance to apoptosis in PASMCs, but not in aortic SMCs.
Conclusion:
By using primary cultures of rat PASMCs and aortic SMCs, we demonstrated that chemerin alone and/or in association with ET-1 induced cellular proliferation and migration and led to resistance to apoptosis. The proliferative and apoptostic responses were PASMCs specific. These in vitro results suggest that chemerin could participate to in vivo pulmonary vascular remodeling, particularly in conditions where ET-1 is upregulated.
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