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学科主题临床医学
Effects of sulfur dioxide on hypoxic pulmonary vascular structural remodeling
Sun, Yan1; Tian, Yue1; Prabha, Mainali1; Liu, Die1; Chen, Stella2; Zhang, Rongyuan1; Liu, Xueqin1; Tang, Chaoshu3,4; Tang, Xiuying5; Jin, Hongfang1; Du, Junbao1,4
关键词glutamate oxaloacetate transaminase inflammation proliferation pulmonary hypertension sulfur dioxide vasoacive peptides
刊名LABORATORY INVESTIGATION
2010
DOI10.1038/labinvest.2009.102
90期:1页:68-82
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, Research & Experimental ; Pathology
研究领域[WOS]Research & Experimental Medicine ; Pathology
关键词[WOS]INHALED NITRIC-OXIDE ; NF-KAPPA-B ; CARBON-MONOXIDE ; HYDROGEN-SULFIDE ; HYPERTENSION ; RATS ; INFLAMMATION ; DERIVATIVES ; CELLS ; H2S
英文摘要

Hypoxic pulmonary hypertension is a pathophysiological process important in the development of various cardiopulmonary diseases. Recently, we found that sulfur dioxide could be produced endogenously by pulmonary vessels, and that it showed vascular regulatory capabilities. In this paper, we examined the role of sulfur dioxide in hypoxic pulmonary vascular structural remodeling (HPVSR). A total of 48 Wistar rats were divided into six groups. Rats in the hypoxic group, hypoxic+sulfur dioxide group, and hypoxic+hydroxamate group were left under hypoxic conditions, whereas the control group, control+sulfur dioxide group, and control+hydroxamate group rats were left in room air. For each group, we measured the pulmonary arterial pressure, sulfur dioxide content in plasma and lung tissue, glutamate oxaloacetate transaminase 1 and 2 mRNAs, micro-and ultra-structural changes in pulmonary arteries, proliferation of pulmonary smooth muscle cells, vascular collagen metabolism, pulmonary endothelial cell inflammatory response, and pulmonary vascular endothelin-1 production in the rats. In hypoxic rats, the content of sulfur dioxide in plasma and lung tissue decreased significantly in comparison with those in the control groups, and significant pulmonary hypertension, pulmonary vascular structural remodeling, and increased vascular inflammatory response were also observed in hypoxic rats. Sulfur dioxide donor significantly downregulated Raf-1, mitogen-activated protein kinase kinase-1 (MEK-1) and p-ERK/ERK, and inhibited pulmonary vascular smooth muscle cell proliferation, collagen remodeling and pulmonary vascular endothelial cell nuclear factor-kappa B (NF-kappa B), and intercellular adhesion molecule 1 (ICAM-1) expressions. It also prevented pulmonary hypertension and pulmonary vascular structural remodeling in association with the upregulated sulfur dioxide/glutamate oxaloacetate transaminase pathway. Hydroxamate, however, advanced pulmonary hypertension, pulmonary vascular structural remodeling, and inflammatory response of the pulmonary artery in association with a downregulated sulfur dioxide/glutamate oxaloacetate transaminase pathway. The results suggested that sulfur dioxide markedly inhibited Raf-1, MEK-1, and the phosphorylation of extracellular signal-regulated kinase (ERK), and then inhibited pulmonary arterial smooth muscle cell (PASMC) proliferation induced by hypoxia. The downregulated sulfur dioxide/glutamate oxaloacetate transaminase pathway may be involved in the mechanisms responsible for pulmonary hypertension and pulmonary vascular structural remodeling. Laboratory Investigation (2010) 90, 68-82; doi:10.1038/labinvest.2009.102; published online 12 October 2009

语种英语
WOS记录号WOS:000273125100009
项目编号20070001702 ; 307001 ; 30630031 ; 30821001 ; 30801251 ; 2006CB503807 ; 7072082
资助机构Ministry of Education, People&prime ; s Republic of China ; National Natural Science Foundation of China ; Major Basic Research Development Program of People&prime ; s Republic of China ; Beijing Natural Science Foundation
引用统计
被引频次:51[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/61200
专题北京大学第一临床医学院_儿科
作者单位1.Minist Educ, Key Lab Mol Cardiol, Beijing, Peoples R China
2.Peking Univ, Dept Pediat, Hosp 1, Beijing 100034, Peoples R China
3.Univ Calif San Diego, La Jolla, CA 92093 USA
4.Peking Univ, Inst Cardiovasc Dis, Hosp 1, Beijing 100034, Peoples R China
5.Peking Univ, Lab Elect Microscope, Hosp 1, Beijing 100034, Peoples R China
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GB/T 7714
Sun, Yan,Tian, Yue,Prabha, Mainali,et al. Effects of sulfur dioxide on hypoxic pulmonary vascular structural remodeling[J]. LABORATORY INVESTIGATION,2010,90(1):68-82.
APA Sun, Yan.,Tian, Yue.,Prabha, Mainali.,Liu, Die.,Chen, Stella.,...&Du, Junbao.(2010).Effects of sulfur dioxide on hypoxic pulmonary vascular structural remodeling.LABORATORY INVESTIGATION,90(1),68-82.
MLA Sun, Yan,et al."Effects of sulfur dioxide on hypoxic pulmonary vascular structural remodeling".LABORATORY INVESTIGATION 90.1(2010):68-82.
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