title: Mitochondrial transplantation attenuates hypoxic pulmonary hypertension.
abstract: Mitochondria are essential for the onset of hypoxia-induced pulmonary vasoconstriction and pulmonary vascular-remodeling, two major aspects underlying the development of pulmonary hypertension, an incurable disease. However, hypoxia induces relaxation of systemic arteries such as femoral arteries and mitochondrial heterogeneity controls the distinct responses of pulmonary versus femoral artery smooth muscle cells to hypoxia in vitro. The aim of this study was to determine whether mitochondrial heterogeneity can be experimentally exploited in vivo for a potential treatment against pulmonary hypertension. The intact mitochondria were transplanted into Sprague-Dawley rat pulmonary artery smooth muscle cells in vivo via intravenous administration. The immune-florescent staining and ultrastructural examinations on pulmonary arteries confirmed the intracellular distribution of exogenous mitochondria and revealed the possible mitochondrial transfer from pulmonary artery endothelial cells into smooth muscle cells in part through their intercellular space and intercellular junctions. The transplantation of mitochondria derived from femoral artery smooth muscle cells inhibited acute hypoxia-triggered pulmonary vasoconstriction, attenuated chronic hypoxia-induced pulmonary vascular remodeling, and thus prevented the development of pulmonary hypertension or cured the established pulmonary hypertension in rats exposed to chronic hypoxia. Our findings suggest that mitochondrial transplantation possesses potential implications for exploring a novel therapeutic and preventive strategy against pulmonary hypertension.
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.|Key Laboratory of Pulmonary Diseases of Ministry of Health, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.|Key Laboratory of Pulmonary Diseases of Ministry of Health, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.|Department of Pathology, Union Hospital, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.|Key Laboratory of Pulmonary Diseases of Ministry of Health, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.|Current address: Department of Clinical Laboratory of Xuzhou Central Hospital, Xuzhou, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.|Key Laboratory of Pulmonary Diseases of Ministry of Health, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.
authors.forename: Yankai
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.|Key Laboratory of Pulmonary Diseases of Ministry of Health, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.
authors.forename: Songling
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.|Key Laboratory of Pulmonary Diseases of Ministry of Health, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xiao
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.|Key Laboratory of Pulmonary Diseases of Ministry of Health, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.
authors.forename: Xiangyuan
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.|Key Laboratory of Pulmonary Diseases of Ministry of Health, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.
authors.forename: Xianqin
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.|Key Laboratory of Pulmonary Diseases of Ministry of Health, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.
authors.forename: Bingxun
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.|Key Laboratory of Pulmonary Diseases of Ministry of Health, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.
authors.forename: Fangbo
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.|Key Laboratory of Pulmonary Diseases of Ministry of Health, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.
authors.forename: Mengxiang
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.|Key Laboratory of Pulmonary Diseases of Ministry of Health, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.
authors.forename: Mao
authors.initials: M
authors.lastname: Dai
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.|Key Laboratory of Pulmonary Diseases of Ministry of Health, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Hao
authors.affiliation: Key Laboratory of Pulmonary Diseases of Ministry of Health, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.|Department of Pathology, Tongji Hospital, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.
authors.forename: Jiansha
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Pulmonary Diseases of Ministry of Health, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.|Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.
authors.forename: Tongfei
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.|Key Laboratory of Pulmonary Diseases of Ministry of Health, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Hu
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D005263:Femoral Artery / Q000473:pathology; D006976:Hypertension, Pulmonary / Q000503:physiopathology / Q000628:therapy*; D000860:Hypoxia / Q000503:physiopathology / Q000628:therapy*; D008928:Mitochondria / Q000378:metabolism* / Q000637:transplantation*; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D011651:Pulmonary Artery / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction
keywords: Pathology Section; hypoxia; mitochondria; pulmonary hypertension; transplantation; vasoconstriction