Visceral adipose tissue-derived serine protease inhibitor prevents the development of monocrotaline-induced pulmonary arterial hypertension in rats
書誌事項
- 公開日
- 2017-08-03
- 資源種別
- journal article
- 権利情報
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- http://www.springer.com/tdm
- http://www.springer.com/tdm
- DOI
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- 10.1007/s00424-017-2043-6
- 公開者
- Springer Science and Business Media LLC
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説明
Visceral adipose tissue-derived serine protease inhibitor (vaspin), a recently identified adipocytokine, inhibits inflammation, migration, and apoptosis of vascular cells. We have recently demonstrated that chronic administration of vaspin to spontaneously hypertensive rats partly prevents systemic hypertension through inhibiting inflammation and remodeling of vascular wall. Pulmonary arterial (PA) hypertension (PAH) is caused by PA remodeling, contractile dysfunction, and inflammatory responses. We tested the hypothesis that vaspin could prevent development of PAH in animal model. PAH was induced by a single intraperitoneal injection of monocrotaline (MCT; 60 mg/kg), and vaspin (1 μg/kg/day) was treated for 14 days from the day of MCT injection. PA pressure and contractile reactivity of isolated intrapulmonary artery (IPA) were measured. Using isolated lung tissues, IPA wall thickness and fibrosis, matrix metalloproteinase (MMP) activity, and reactive oxygen species (ROS) generation were examined. For in vitro study, after rat PA smooth muscle cells (PASMCs) were stimulated with interleukin (IL)-1β (10 ng/ml, 48 h) in the presence of vaspin (5 ng/ml, 30 min), MMP activity and ROS generation were examined. Vaspin significantly attenuated MCT-induced rise in PA pressure, while it had no influence on impairment of relaxing function in IPA. Vaspin significantly prevented MCT-induced IPA fibrosis but not hypertrophy. Vaspin significantly inhibited MCT-induced ROS generation and MMP-2 activation in lung tissues. In addition, vaspin significantly inhibited IL-1β-induced ROS generation and MMP-2 activation in PASMCs. In summary, we for the first time demonstrate that vaspin prevents MCT-induced PAH at least in part via inhibiting ROS/MMP-2/fibrosis pathway.
収録刊行物
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- Pflügers Archiv - European Journal of Physiology
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Pflügers Archiv - European Journal of Physiology 469 (11), 1425-1432, 2017-08-03
Springer Science and Business Media LLC
