Fractalkine-induced smooth muscle cell proliferation in pulmonary hypertension

¹ 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, Clamart, France; and Institut National de la Santé et de la Recherche Médicale, U764, Institut Fédératif de Recherche 13, Clamart, France
² 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, Clamart, France
³ Institut National de la Santé et de la Recherche Médicale, U764, Institut Fédératif de Recherche 13, Clamart, France
⁴ INSERM U651, Université Paris 12, Créteil, France
⁵ UPRES EA2705, Laboratoire de Chirurgie Expérimentale, Centre Chirurgical Marie Lannelongue, Université Paris-Sud 11, Le Plessis Robinson, France

^* To whom correspondence should be addressed. E-mail: marc.humbert{at}abc.aphp.fr.

	Abstract

Pulmonary hypertension is characterized 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 this study was to address the role of fractalkine (CX3CL1) in the inflammatory responses and in the pulmonary vascular remodeling of a monocrotaline-induced pulmonary hypertension model.

We studied the expression of CX3CL1 and its receptor CX3CR1 in monocrotaline-induced pulmonary hypertension by means of immunohistochemistry and quantitative reverse-transcription polymerase chain reaction on laser-captured microdissected pulmonary arteries.

We demonstrated that CX3CL1 was expressed by inflammatory cells surrounding pulmonary arterial lesions and that smooth muscle cells from these vessels had increased CX3CR1 expression. Then we showed that cultured rat pulmonary artery smooth muscle cells expressed CX3CR1 and that CX3CL1 induced proliferation but not migration of these cells. Conclusions: We propose that fractalkine may act as a growth factor for pulmonary artery smooth muscle cells. Chemokines may thus play a role in pulmonary artery remodeling.

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