Fractalkine-induced smooth muscle cell proliferation in pulmonary hypertension.
Pulmonary hypertension is characterised by a progressive increase in pulmonary arterial resistance due to endothelial and smooth muscle cell proliferation resulting in chronic obstruction of small pulmonary arteries. There is evidence that inflammatory mechanisms may contribute to the pathogenesis of human and experimental pulmonary hypertension. The aim of the study was to address the role of fractalkine (CX3CL1) in the inflammatory responses and pulmonary vascular remodelling of a monocrotaline-induced pulmonary hypertension model. The expression of CX3CL1 and its receptor CX3CR1 was studied in monocrotaline-induced pulmonary hypertension by means of immunohistochemistry and quantitative reverse-transcription PCR on laser-captured microdissected pulmonary arteries. It was demonstrated that CX3CL1 was expressed by inflammatory cells surrounding pulmonary arterial lesions and that smooth muscle cells from these vessels had increased CX3CR1 expression. It was then shown that cultured rat pulmonary artery smooth muscle cells expressed CX3CR1 and that CX3CL1 induced proliferation but not migration of these cells. In conclusion, the current authors proposed that fractalkine may act as a growth factor for pulmonary artery smooth muscle cells. Chemokines may thus play a role in pulmonary artery remodelling.
Perros
F
F
UPRES EA2705, Service de Pneumologie, Centre National de Référence de l'Hypertension Artérielle Pulmonaire, Hôpital Antoine-Béclère, Assistance-Publique Hôpitaux de Paris, Université Paris-Sud 11, Robinson, France.
Dorfmüller
P
P
Souza
R
R
Durand-Gasselin
I
I
Godot
V
V
Capel
F
F
Adnot
S
S
Eddahibi
S
S
Mazmanian
M
M
Fadel
E
E
Hervé
P
P
Simonneau
G
G
Emilie
D
D
Humbert
M
M
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000378:metabolism*; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515540:Cx3cl1 protein, rat; D008565:Membrane Proteins