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学科主题: 临床医学
题名:
Effects of endogenous carbon monoxide on collagen synthesis in pulmonary artery in rats under hypoxia
作者: Gong, LM; Du, JB; Shi, L; Shi, Y; Tang, CS
关键词: carbon monoxide ; hypoxia ; pulmonary hypertension ; collagen synthesis ; transforming growth factor-beta
刊名: LIFE SCIENCES
发表日期: 2004-01-23
DOI: 10.1016/j.lfs.2003.07.046
卷: 74, 期:10, 页:1225-1241
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Medicine, Research & Experimental ; Pharmacology & Pharmacy
研究领域[WOS]: Research & Experimental Medicine ; Pharmacology & Pharmacy
关键词[WOS]: GROWTH-FACTOR-BETA ; SMOOTH-MUSCLE-CELLS ; HEME OXYGENASE ACTIVITY ; NITRIC-OXIDE ; EXTRACELLULAR-MATRIX ; ZINC-PROTOPORPHYRIN ; HYPERTENSIVE RATS ; EXPRESSION ; MECHANISMS ; PROLIFERATION
英文摘要:

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-beta(3) (TGF-beta(3)) expressions were detected by immunohistochemical assay. The expressions of procollagen type I and III and TGF-beta(3) 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-β(3) 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-beta(3) 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-β(3). The above findings also suggested a possible role of endogenous CO in the pathogenesis of chronic hypoxic pulmonary hypertension. (C) 2003 Elsevier Inc. All rights reserved.

语种: 英语
WOS记录号: WOS:000187964800004
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56820
Appears in Collections:北京大学第一临床医学院_儿科_期刊论文

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作者单位: 1.Peking Univ, Hosp 1, Dept Pediat, Beijing 100034, Peoples R China
2.Peking Univ, Hosp 1, Inst Cardiovasc Dis, Beijing 100871, Peoples R China

Recommended Citation:
Gong, LM,Du, JB,Shi, L,et al. Effects of endogenous carbon monoxide on collagen synthesis in pulmonary artery in rats under hypoxia[J]. LIFE SCIENCES,2004,74(10):1225-1241.
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