title: Calcium signalling induced by in vitro exposure to silicium dioxide nanoparticles in rat pulmonary artery smooth muscle cells.
abstract: The development and use of nanomaterials, especially engineered nanoparticles (NP), is expected to provide many benefits. But at the same time the development of such materials is also feared because of their potential human health risks. Indeed, NP display some characteristics similar to ultrafine environmental particles which are known to exert deleterious cardiovascular effects including pro-hypertensive ones. In this context, the effect of NP on calcium signalling, whose deregulation is often involved in hypertensive diseases, remain poorly described. We thus assessed the effect of SiO2NP on calcium signalling by fluorescence imaging and on the proliferation response in rat pulmonary artery smooth muscle cells (PASMC). In PASMC, acute exposure to SiO2NP, from 1 to 500μg/mL, produced an increase of the [Ca2+]i. In addition, when PASMC were exposed to NP at 200μg/mL, a proliferative response was observed. This calcium increase was even greater in PASMC isolated from rats suffering from pulmonary hypertension. The absence of extracellular calcium, addition of diltiazem or nicardipine (L-type voltage-operated calcium channel inhibitors both used at 10μM), and addition of capsazepine or HC067047 (TRPV1 and TRPV4 inhibitors used at 10μM and 5μM, respectively) significantly reduced this response. Moreover, this response was also inhibited by thapsigargin (SERCA inhibitor, 1μM), ryanodine (100μM) and dantrolene (ryanodine receptor antagonists, 10μM) but not by xestospongin C (IP3receptor antagonist, 10μM). Thus, NP induce an intracellular calcium rise in rat PASMC originating from both extracellular and intracellular calcium sources. This study also provides evidence for the implication of TRPV channels in NP induced calcium rise that may highlight the role of these channels in the deleterious cardiovascular effects of NP.
authors.affiliation: Université de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France; Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France. Electronic address: cubitus2@hotmail.fr.
authors.forename: Virginie
authors.initials: V
authors.lastname: Dubes
authors.affiliation: Université de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France; Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France. Electronic address: cocal@hotmail.fr.
authors.forename: Thibaud
authors.initials: T
authors.lastname: Parpaite
authors.affiliation: Université de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France; Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France. Electronic address: thomas.ducret@u-bordeaux.fr.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ducret
authors.affiliation: Université de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France; Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France. Electronic address: jean-francois.quignard@u-bordeaux.fr.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Quignard
authors.affiliation: Université de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France; CNRS, ICMCB, UPR 9048, 87 Avenue du Dr Albert Schweitzer, 33600 Pessac, France. Electronic address: stephane.mornet@icmcb.cnrs.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Mornet
authors.affiliation: Université de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France; CNRS, ICMCB, UPR 9048, 87 Avenue du Dr Albert Schweitzer, 33600 Pessac, France. Electronic address: nora.reinhardt@icmcb.cnrs.fr.
authors.forename: Nora
authors.initials: N
authors.lastname: Reinhardt
authors.affiliation: Université de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France; Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France. Electronic address: isabelle.baudrimont@u-bordeaux.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Baudrimont
authors.affiliation: Université de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France; Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France. Electronic address: mathilde.dubois@u-bordeaux.fr.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Dubois
authors.affiliation: Université de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France; Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France. Electronic address: veronique.michel@u-bordeaux.fr.
authors.forename: Véronique
authors.initials: V
authors.lastname: Freund-Michel
authors.affiliation: Université de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France; Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France; Centre Hospitalier Universitaire de Bordeaux, Hôpital du Haut-Lévêque, Service d'Exploration Fonctionnelle Respiratoire, Avenue de Magellan, Pessac, F-33076, France. Electronic address: roger.marthan@u-bordeaux.fr.
authors.forename: Roger
authors.initials: R
authors.lastname: Marthan
authors.affiliation: Université de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France; Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France. Electronic address: bernard.muller@u-bordeaux.fr.
authors.forename: Bernard
authors.initials: B
authors.lastname: Muller
authors.affiliation: Université de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France; Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France. Electronic address: jean-pierre.savineau@u-bordeaux.fr.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Savineau
authors.affiliation: Université de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France; Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, 146, rue Léo Saignat, Bordeaux, F-33076, France; Centre Hospitalier Universitaire de Bordeaux, Centre AntiPoison et de Toxicovigilance d'Aquitaine et de Poitou Charente, Place Amélie Raba Léon, Bordeaux, F-33076, France. Electronic address: arnaud.courtois@u-bordeaux.fr.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Courtois
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D053758:Nanoparticles / Q000633:toxicity*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012822:Silicon Dioxide / Q000633:toxicity*
chemical_list: D012822:Silicon Dioxide
keywords: Intracellular calcium; Rat pulmonary artery smooth muscle cells; SiO(2) nanoparticles; Transient receptor potential vanilloid channels