| Effects of endogenous carbon monoxide on collagen synthesis in pulmonary artery in rats under hypoxia. | |
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MedLine Citation:
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PMID: 14697406 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To study the role of endogenous carbon monoxide (CO) in collagen metabolism during hypoxic pulmonary vascular remodeling, a total of 18 Wistar rats were used in the study and they were randomly divided into three groups: hypoxia group (n = 6), hypoxia with zinc protoporphyrin-IX (ZnPP-IX) group (n = 6) and control group (n = 6). The measurement of mean pulmonary artery pressure (mPAP) and carboxyhemoglobin (HbCO) formation in lung tissue homogenates was measured. A morphometric analysis of pulmonary vessels was performed, in which the percentage of muscularized arteries (MA); partially muscularized arteries (PMA) and nonmuscularized arteries (NMV) in small and median pulmonary vessels, relative medial thickness (RMT) and relative medial area (RMA) of pulmonary arteries were analyzed. Collagen type I and III and transforming growth factor-beta3 (TGF-beta3) expressions were detected by immunohistochemical assay. The expressions of procollagen type I and III and TGF-beta3 mRNA were detected by in situ hybridization. The results showed that ZnPP-IX significantly increased mPAP and markedly decreased HbCO formation in lung tissue homogenates in rats under hypoxia (P < 0.01). In the hypoxia rats treated with ZnPP-IX, the percentage of muscularized arteries of small and median pulmonary vessels was obviously increased, and RMT and RMA of intra-acinar muscularized pulmonary arteries were markedly increased compared with hypoxic rats. Ultrastructural changes, such as hyperplasia and hypertrophy of endothelial cells (ECs) and smooth muscle cells (SMCs) and the increased number of SMCs in synthetic phenotype were found in intra-acinar pulmonary muscularized arteries of hypoxic rats treated with ZnPP-IX. Meanwhile, ZnPP-IX promoted the expression of collagen type I and III and TGF-beta3 protein in pulmonary arteries of rats under hypoxia (P < 0.01). Furthermore, ZnPP-IX elevated obviously the expressions of procollagen type I and III mRNA, and TGF-beta3 mRNA in pulmonary arteries of rats under hypoxia (P < 0.01). The results of this study suggested that ZnPP-IX played an important role in promoting collagen synthesis in pulmonary arteries of rats with hypoxic pulmonary structural remodeling by increasing the expression of TGF-beta3. The above findings also suggested a possible role of endogenous CO in the pathogenesis of chronic hypoxic pulmonary hypertension. |
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Authors:
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Li-min Gong; Jun-bao Du; Lin Shi; Yun Shi; Chao-shu Tang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Life sciences Volume: 74 ISSN: 0024-3205 ISO Abbreviation: Life Sci. Publication Date: 2004 Jan |
Date Detail:
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Created Date: 2003-12-30 Completed Date: 2004-02-23 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0375521 Medline TA: Life Sci Country: England |
Other Details:
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Languages: eng Pagination: 1225-41 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, First Hospital of Peking University, Xi An Men Street No. 1, Beijing 100034, PR China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Algorithms Animals Anoxia / metabolism* Blood Pressure / drug effects, physiology Carbon Monoxide / metabolism, physiology* Collagen / biosynthesis* Elasticity Enzyme Inhibitors / pharmacology Heme Oxygenase (Decyclizing) / antagonists & inhibitors Immunohistochemistry In Situ Hybridization Lung / anatomy & histology, metabolism Male Muscle, Smooth, Vascular / cytology, metabolism Protoporphyrins / pharmacology Pulmonary Artery / metabolism*, ultrastructure Pulmonary Wedge Pressure / physiology RNA, Messenger / biosynthesis Rats Rats, Wistar Transforming Growth Factor alpha / biosynthesis |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Protoporphyrins; 0/RNA, Messenger; 0/Transforming Growth Factor alpha; 15442-64-5/zinc protoporphyrin; 630-08-0/Carbon Monoxide; 9007-34-5/Collagen; EC 1.14.99.3/Heme Oxygenase (Decyclizing) |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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