title: Proteomic analysis of vascular smooth muscle cells in physiological condition and in pulmonary arterial hypertension: Toward contractile versus synthetic phenotypes.
abstract: Vascular smooth muscle cells (VSMCs) are highly specialized cells that regulate vascular tone and participate in vessel remodeling in physiological and pathological conditions. It is unclear why certain vascular pathologies involve one type of vessel and spare others. Our objective was to compare the proteomes of normal human VSMC from aorta (human aortic smooth muscle cells, HAoSMC), umbilical artery (human umbilical artery smooth muscle cells, HUASMC), pulmonary artery (HPASMC), or pulmonary artery VSMC from patients with pulmonary arterial hypertension (PAH-SMC). Proteomes of VSMC were compared by 2D DIGE and MS. Only 19 proteins were differentially expressed between HAoSMC and HPASMC while 132 and 124 were differentially expressed between HUASMC and HAoSMC or HPASMC, respectively (fold change 1.5≤ or -1.5≥, p < 0.05). As much as 336 proteins were differentially expressed between HPASMC and PAH-SMC (fold change 1.5≤ or -1.5≥, p < 0.05). HUASMC expressed increased amount of α-smooth muscle actin compared to either HPASMC or HAoSMC (although not statistically significant). In addition, PAH-SMC expressed decreased amount of smooth muscle myosin heavy chain and proliferation rate was increased compared to HPASMC thus supporting that PAH-SMC have a more synthetic phenotype. Analysis with Ingenuity identified paxillin and (embryonic lethal, abnormal vision, drosophila) like 1 (ELAVL1) as molecules linked with a lot of proteins differentially expressed between HPASMC and PAH-SMC. There was a trend toward reduced proliferation of PAH-SMC with paxillin-si-RNA and increased proliferation with ELAVL1-siRNA. Thus, VSMCs have very diverse protein content depending on their origin and this is in link with phenotypic differentiation. Paxillin targeting may be a promising treatment of PAH. ELAVL1 also participate in the regulation of PAH-SMC proliferation.
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, LabEx INFLAMEX, Université Paris Descartes, Paris, France.|Service de Médecine Interne, Centre de Référence pour les vascularites nécrosantes et la sclérodermie systémique, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Régent
authors.affiliation: Service de Médecine Interne A, CHU Dupuytren, Limoges, France.
authors.forename: Kim Heang
authors.initials: KH
authors.lastname: Ly
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, LabEx INFLAMEX, Université Paris Descartes, Paris, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lofek
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, LabEx INFLAMEX, Université Paris Descartes, Paris, France.|Plate-forme Protéomique 3P5, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Guilhem
authors.initials: G
authors.lastname: Clary
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, LabEx INFLAMEX, Université Paris Descartes, Paris, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Tamby
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, LabEx INFLAMEX, Université Paris Descartes, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tamas
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, LabEx INFLAMEX, Université Paris Descartes, Paris, France.|Plate-forme Protéomique 3P5, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Federici
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, LabEx INFLAMEX, Université Paris Descartes, Paris, France.|Plate-forme Protéomique 3P5, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Broussard
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, LabEx INFLAMEX, Université Paris Descartes, Paris, France.|Plate-forme Protéomique 3P5, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Chafey
authors.affiliation: IRCM, Institut de Recherche en Cancérologie de Montpellier; INSERM, U1194, Université de Montpellier, Institut régional du Cancer de Montpellier, Montpellier, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Liaudet-Coopman
authors.affiliation: Faculté de Médecine, Université Paris-Sud, Le Kremlin-Bicêtre, France.|INSERM UMR-S 999, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, LabEx LERMIT, Le Plessis-Robinson, France.|Centre Chirurgical Marie Lannelongue, Département de Recherche Médicale, Le Plessis-Robinson, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
authors.affiliation: Faculté de Médecine, Université Paris-Sud, Le Kremlin-Bicêtre, France.|INSERM UMR-S 999, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, LabEx LERMIT, Le Plessis-Robinson, France.|Centre Chirurgical Marie Lannelongue, Département de Recherche Médicale, Le Plessis-Robinson, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Perros
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, LabEx INFLAMEX, Université Paris Descartes, Paris, France. luc.mouthon@aphp.fr.|Service de Médecine Interne, Centre de Référence pour les vascularites nécrosantes et la sclérodermie systémique, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France. luc.mouthon@aphp.fr.
authors.forename: Luc
authors.initials: L
authors.lastname: Mouthon
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D000067780:ELAV-Like Protein 1 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology*; D051419:Paxillin / Q000235:genetics / Q000378:metabolism; D060066:Protein Interaction Maps; D020543:Proteome / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D051419:Paxillin; D020543:Proteome; D034741:RNA, Small Interfering
keywords: Cell biology; ELAVL1; Paxillin; Pulmonary hypertension; Vascular smooth muscle cell