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	Peripheral arterial occlusive disease: global gene expression analyses suggest a major role for immune and inflammatory responses
	Fu, Shijun2,12; Zhao, Haiguang3; Shi, Jiantao2,12; Abzhanov, Arhat1,7; Crawford, Keith1,10; Ohno-Machado, Lucila1,9; Zhou, Jianqin11; Du, Yanzhi2; Kuo, Winston Patrick1,7,8,9; Zhang, Ji2
刊名	Bmc genomics
	2008-08-01
卷号	9页码:18
ISSN号	1471-2164
DOI	10.1186/1471-2164-9-369
通讯作者	Kuo, winston patrick(winston_kuo@hsdm.harvard.edu)
英文摘要	Background: peripheral arterial disease (pad), a major manifestation of atherosclerosis, is associated with significant cardiovascular morbidity, limb loss and death. however, mechanisms underlying the genesis and progression of the disease are far from clear. genome-wide gene expression profiling of clinical samples may represent an effective approach to gain relevant information. results: after histological classification, a total of 30 femoral artery samples, including 11 intermediate lesions, 14 advanced lesions and 5 normal femoral arteries, were profiled using affymetrix microarray platform. following real-time rt-pcr validation, different algorithms of gene selection and clustering were applied to identify differentially expressed genes. under a stringent cutoff, i. e., a false discovery rate (fdr) < 0.5%, we found 366 genes were differentially regulated in intermediate lesions and 447 in advanced lesions. of these, 116 genes were overlapped between intermediate and advanced lesions, including 68 up-regulated genes and 48 down-regulated ones. in these differentially regulated genes, immune/inflammatory genes were significantly up-regulated in different stages of pad, (85/230 in intermediate lesions, 37/172 in advanced lesions). through literature mining and pathway analysis using different databases such as gene ontology (go), and the kyoto encyclopedia of gene and genomics (kegg), genes involved in immune/inflammatory responses were significantly enriched in up-regulated genes at different stages of pad(p < 0.05), revealing a significant correlation between immune/inflammatory responses and disease progression. moreover, immune-related pathways such as toll-like receptor signaling and natural killer cell mediated cytotoxicity were particularly enriched in intermediate and advanced lesions (p < 0.05), highlighting their pathogenic significance during disease progression. conclusion: lines of evidence revealed in this study not only support previous hypotheses, primarily based on studies of animal models and other types of arterial disease, that inflammatory responses may influence the development of pad, but also permit the recognition of a wide spectrum of immune/inflammatory genes that can serve as signatures for disease progression in pad. further studies of these signature molecules may eventually allow us to develop more sophisticated protocols for pharmaceutical interventions.
WOS关键词	TOLL-LIKE RECEPTOR-2 ; TRANSCRIPTION FACTORS ; APOLIPOPROTEIN-E ; KNOCKOUT MICE ; C-JUN ; ATHEROSCLEROSIS ; PATHWAY ; CELLS ; MACROPHAGES ; ACTIVATION
WOS研究方向	Biotechnology & Applied Microbiology ; Genetics & Heredity
WOS类目	Biotechnology & Applied Microbiology ; Genetics & Heredity
语种	英语
出版者	BIOMED CENTRAL LTD
WOS记录号	WOS:000259137500001
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2385121
专题	中国科学院大学
通讯作者	Kuo, Winston Patrick
作者单位	1.Harvard Univ, Sch Dent Med, Lab Innovat Translat Technol, Boston, MA 02115 USA 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Shanghai, Peoples R China 3.Shanghai Jiao Tong Univ, Sch Med, Shanghai Ninth Peoples Hosp, Shanghai 200030, Peoples R China 4.ShanghaiBio Corp, N Brunswick, NJ USA 5.Shanghai Biochip Co Ltd, Shanghai, Peoples R China 6.Natl Engn Ctr Biochip Shanghai, Shanghai, Peoples R China 7.Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA 8.Harvard Sch Dent Med, Dept Dev Biol, Boston, MA USA 9.Harvard Univ, Brigham & Womens Hosp, Sch Med, Decis Syst Grp, Boston, MA 02115 USA 10.Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped, Boston, MA 02115 USA
推荐引用方式 GB/T 7714	Fu, Shijun,Zhao, Haiguang,Shi, Jiantao,et al. Peripheral arterial occlusive disease: global gene expression analyses suggest a major role for immune and inflammatory responses[J]. Bmc genomics,2008,9:18.
APA	Fu, Shijun.,Zhao, Haiguang.,Shi, Jiantao.,Abzhanov, Arhat.,Crawford, Keith.,...&Jin, Jason Gang.(2008).Peripheral arterial occlusive disease: global gene expression analyses suggest a major role for immune and inflammatory responses.Bmc genomics,9,18.
MLA	Fu, Shijun,et al."Peripheral arterial occlusive disease: global gene expression analyses suggest a major role for immune and inflammatory responses".Bmc genomics 9(2008):18.

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