title: PAF-receptor is preferentially expressed in a distinct synthetic phenotype of smooth muscle cells cloned from human internal thoracic artery: functional implications in cell migration.
abstract: Platelet-activating-Factor (PAF) and its structural analogues formed upon low density lipoprotein oxidation are involved in atherosclerotic plaque formation and may signal through PAF-receptor (PAF-R) expressed in human macrophages and in certain smooth muscle cells (SMCs) in the media, but rarely in the intima of human plaques. Our aim was to determine which SMC phenotype expresses PAF-R and whether this receptor is functional in cell migration. Circulating SMC progenitors and two phenotypically distinct clones of proliferative, epithelioid phenotype vs contractile, spindle-shaped SMCs from the media of adult internal thoracic artery were studied for the presence of PAF-receptor (PAF-R). The levels of specific mRNA were obtained by reverse transcription/real-time PCR, the protein expression was deduced from immunohistochemistry staining, and the functional transmigration assay was performed by Boyden chamber-type chemotaxis assay. Only SMCs of spindle-shape and synthetic phenotype expressed both mRNA and PAF-R protein and in the functional test migrated at low concentrations of PAF. Two unrelated, specific PAF-R antagonists inhibited PAF-induced migration, but did not modify the migration initiated by PDGF. The presence of functional PAF-R in arterial spindle-shaped SMCs of synthetic phenotype may be important for their migration from the media into the intima and atherosclerotic plaques formation.
authors.affiliation: INSERM U525, Institut Fédératif CMV, Université Pierre et Marie Curie-Paris6, Faculté de Médecine Pierre et Marie Curie, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Stengel
authors.forename: Caroline
authors.initials: C
authors.lastname: O'Neil
authors.forename: Isabelle
authors.initials: I
authors.lastname: Brochériou
authors.forename: Sonia-Athina
authors.initials: SA
authors.lastname: Karabina
authors.forename: Hervé
authors.initials: H
authors.lastname: Durand
authors.forename: Noel M
authors.initials: NM
authors.lastname: Caplice
authors.forename: J Geoffrey
authors.initials: JG
authors.lastname: Pickering
authors.forename: Ewa
authors.initials: E
authors.lastname: Ninio
mesh_terms: D002465:Cell Movement; D002999:Clone Cells / Q000166:cytology* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008323:Mammary Arteries / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism*; D010641:Phenotype; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
chemical_list: D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor