title: Chronic hypoxia aggravates monocrotaline-induced pulmonary arterial hypertension: a rodent relevant model to the human severe form of the disease.
abstract: Pulmonary arterial hypertension (PAH) is a severe form of pulmonary hypertension that combines multiple alterations of pulmonary arteries, including, in particular, thrombotic and plexiform lesions. Multiple-pathological-insult animal models, developed to more closely mimic this human severe PAH form, often require complex and/or long experimental procedures while not displaying the entire panel of characteristic lesions observed in the human disease. In this study, we further characterized a rat model of severe PAH generated by combining a single injection of monocrotaline with 4 weeks exposure to chronic hypoxia. This model displays increased pulmonary arterial pressure, right heart altered function and remodeling, pulmonary arterial inflammation, hyperresponsiveness and remodeling. In particular, severe pulmonary arteriopathy was observed, with thrombotic, neointimal and plexiform-like lesions similar to those observed in human severe PAH. This model, based on the combination of two conventional procedures, may therefore be valuable to further understand the pathophysiology of severe PAH and identify new potential therapeutic targets in this disease.
authors.affiliation: INSERM, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France. florence-coste@hotmail.fr.|Univ. Bordeaux, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France. florence-coste@hotmail.fr.|CHU de Bordeaux, F-33000, Bordeaux, France. florence-coste@hotmail.fr.
authors.forename: Florence
authors.identifier: 0000-0001-5858-8327
authors.initials: F
authors.lastname: Coste
authors.affiliation: INSERM, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.|Univ. Bordeaux, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Guibert
authors.affiliation: INSERM, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.|Univ. Bordeaux, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.|IHU Liryc, Electrophysiology and Heart Modeling Institute, fondation Bordeaux Université, F-33600, Pessac, Bordeaux, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Magat
authors.affiliation: INSERM, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.|Univ. Bordeaux, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.|IHU Liryc, Electrophysiology and Heart Modeling Institute, fondation Bordeaux Université, F-33600, Pessac, Bordeaux, France.
authors.forename: Emma
authors.initials: E
authors.lastname: Abell
authors.affiliation: INSERM, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.|Univ. Bordeaux, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.|IHU Liryc, Electrophysiology and Heart Modeling Institute, fondation Bordeaux Université, F-33600, Pessac, Bordeaux, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Vaillant
authors.affiliation: INSERM, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.|Univ. Bordeaux, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Dubois
authors.affiliation: INSERM, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.|Univ. Bordeaux, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Courtois
authors.affiliation: INSERM, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.|Univ. Bordeaux, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.|IHU Liryc, Electrophysiology and Heart Modeling Institute, fondation Bordeaux Université, F-33600, Pessac, Bordeaux, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Diolez
authors.affiliation: INSERM, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.|Univ. Bordeaux, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.|IHU Liryc, Electrophysiology and Heart Modeling Institute, fondation Bordeaux Université, F-33600, Pessac, Bordeaux, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Quesson
authors.affiliation: INSERM, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.|Univ. Bordeaux, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.|CHU de Bordeaux, F-33000, Bordeaux, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Marthan
authors.affiliation: INSERM, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.|Univ. Bordeaux, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Savineau
authors.affiliation: INSERM, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.|Univ. Bordeaux, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Muller
authors.affiliation: INSERM, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.|Univ. Bordeaux, Centre de recherche Cardio-Thoracique de Bordeaux U1045, F-33000, Bordeaux, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Freund-Michel
mesh_terms: D000818:Animals; D062186:Arterial Pressure; D002908:Chronic Disease; D004195:Disease Models, Animal; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology*; D008297:Male; D016686:Monocrotaline; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D016686:Monocrotaline
keywords: Animal model; Plexiform-like lesions; Pulmonary arterial hypertension