Journal
ONCOTARGET
Volume 7, Issue 31, Pages 48925-48940Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.10596
Keywords
Hypoxia; mitochondria; transplantation; pulmonary hypertension; vasoconstriction; remodeling; Pathology Section
Categories
Funding
- National Natural Science Foundation of China [81170048, 81330001, 81400027, 30971162, 81470252, 81170049, 31270031, 31400990, 81572274, 30900545, 31371422, 81370176]
- State Key Laboratory of Respiratory Disease [SKLRD2016OP001]
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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..
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