title: Development and characterization of an animal model of severe pulmonary arterial hypertension.
abstract: Pulmonary arterial hypertension (PAH) is a serious pathological phenomenon with poor prognosis, which is associated with morphological as well as hemodynamic alteration of the pulmonary circulation. To establish an animal model mimicking severe human PAH, we combined 2 well-described procedures, i.e. exposure to hypobaric chronic hypoxia and administration of monocrotaline hydrochloride in rats. Compared to a single procedure, the combined procedure induced more severe right ventricle hypertrophy and an increase in right ventricle systolic pressure. Histological examination on the combined procedure model revealed a severe medial hypertrophy as well as occlusive vascular changes of the intra-acinar pulmonary arteries with endothelial lesions. It is noteworthy that severe alterations including concentric neointimal thickening, abnormal endothelial proliferation, plexiform lesions and vascular occlusion with fibrin thrombi were observed in the combined pulmonary hypertension model when exposed to a long period of hypoxia. The present data indicate that a combined treatment of monocrotaline injection and hypobaric chronic hypoxia exposure produces more severe hemodynamic changes and histological alterations. Since human PAH diagnosed in clinical practice is often severe, this combined treatment animal model could be useful to identify relevant therapeutic targets acting on both hemodynamic and structural alterations of the pulmonary circulation.
authors: Department of Cell Pathology, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
authors: Yoshitaka
authors: Y
authors: Morimatsu
authors: Naomi
authors: N
authors: Sakashita
authors: Yoshihiro
authors: Y
authors: Komohara
authors: Koji
authors: K
authors: Ohnishi
authors: Hiroshi
authors: H
authors: Masuda
authors: Diana
authors: D
authors: Dahan
authors: Motohiro
authors: M
authors: Takeya
authors: Christelle
authors: C
authors: Guibert
authors: Roger
authors: R
authors: Marthan
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D065627:Familial Primary Pulmonary Hypertension; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications; D008297:Male; D016686:Monocrotaline / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D017540:Tunica Media / Q000473:pathology
chemical_list: D016686:Monocrotaline