| DOWNREGULATION OF OSTEOPONTIN IS ASSOCIATED WITH FLUOXETINE AMELIORATION OF MONOCROTALINE-INDUCED PULMONARY INFLAMMATION AND VASCULAR REMODELLING. | |
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MedLine Citation:
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PMID: 21418086 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Osteopontin (OPN) has emerged as a key factor in inflammatory activation and cardiovascular remodelling. The aim of the present study was to investigate the involvement of OPN in fluoxetine amelioration of monocrotaline (MCT)-induced pulmonary inflammation and vascular remodelling in rats. Wistar rats were divided into control, MCT and two fluoxetine-treated groups. Pulmonary arterial hypertension (PAH) was induced by a single injection of MCT (60 mg/kg, i.p.). Fluoxetine (2 and 10 mg/kg) was administered via the intragastric route once a day for 21 days. On Day 22, pulmonary haemodynamic measurements were undertaken, followed by ELISA, western blotting and immunohistochemistry. Monocrotaline caused pulmonary inflammation and vascular remodelling and significantly enhanced OPN expression in the plasma, lungs and pulmonary arteries. Fluoxetine decreased pulmonary arterial pressure and ameliorated pulmonary inflammation and pulmonary vascular remodelling. At 10 mg/kg, fluoxetine significantly inhibited MCT-induced increases in the expression of serotonin transporter (SERT) and phosphorylated extracellular signal-regulated kinase 1/2 and downregulated the expression of OPN, macrophage inflammatory protein-1β and matrix metalloproteinase 2/tissue inhibitor of metalloproteinase 2. Although 2 mg/kg fluoxetine tended to ameliorate some MCT-induced changes in the lung, the differences did not always reach statistical significance. Linear regression analysis showed that there was a positive correlation between plasma OPN concentrations and mean pulmonary arterial pressure, as well as percentage medial wall thickness and percentage wall area in the pulmonary artery. In conclusion, the amelioration by fluoxetine of MCT-induced pulmonary inflammation and vascular remodelling is associated with downregulation of OPN expression in rats. |
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Authors:
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Yun Wang; Dan-Dan Han; Han-Ming Wang; Ming Liu; Xin-Hua Zhang; Huai-Liang Wang |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-19 |
Journal Detail:
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Title: Clinical and experimental pharmacology & physiology Volume: - ISSN: 1440-1681 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-22 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0425076 Medline TA: Clin Exp Pharmacol Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd. |
Affiliation:
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Department of Clinical Pharmacology, China Medical University, Shenyang, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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