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学科主题: 基础医学
题名:
Hyperhomocysteinemia Exaggerates Adventitial Inflammation and Angiotensin II-Induced Abdominal Aortic Aneurysm in Mice
作者: Liu, Ziyi2; Luo, Hongzhi2; Zhang, Lu; Huang, Yaqian2; Liu, Bo2; Ma, Kongyang2; Feng, Juan2; Xie, Jinsheng3; Zheng, Jingang4; Hu, Jing5; Zhan, Siyan5; Zhu, Yi2; Xu, Qingbo6; Kong, Wei1,2; Wang, Xian1,2
关键词: abdominal aortic aneurysm ; adventitial fibroblast ; hyperhomocysteinemia ; NADPH oxidase 4
刊名: CIRCULATION RESEARCH
发表日期: 2012-10-26
DOI: 10.1161/CIRCRESAHA.112.270520
卷: 111, 期:10, 页:1261-U96
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cardiac & Cardiovascular Systems ; Hematology ; Peripheral Vascular Disease
研究领域[WOS]: Cardiovascular System & Cardiology ; Hematology
关键词[WOS]: PLASMA HOMOCYSTEINE ; FOLIC-ACID ; VASCULAR-DISEASE ; RISK-FACTOR ; CAPTOPRIL-HYDROCHLOROTHIAZIDE ; ACCELERATED ATHEROSCLEROSIS ; DEFICIENT MICE ; OXIDASE ; STRESS ; DIFFERENTIATION
英文摘要:

Rationale: A number of epidemiological studies have suggested an association of hyperhomocysteinemia (HHcy) and abdominal aortic aneurysm (AAA), but discrepancies exist. In addition, we lack direct evidence supporting a causal role.

Objective: We determined the association and contribution of HHcy to AAA formation.

Methods and Results: We first performed a meta-analysis of studies involving 1489 subjects and found a strong association of HHcy and AAA (odds ratio, 7.39). Next, we used angiotensin II-infused male apolipoprotein E-deficient mice and tested whether HHcy contributes to AAA pathogenesis. Homocysteine (Hcy) supplement (1.8 g/L) in drinking water resulted in mild HHcy. Intriguingly, HHcy greatly increased the incidence of angiotensin II-induced AAA and aortic dissection in apolipoprotein E-deficient mice (vehicle versus Hcy: 50% versus 100%; P<0.05). Histology indicated HHcy markedly exaggerated aortic adventitial inflammation. Increased levels of proinflammatory interleukin-6 and monocyte chemoattractant protein-1 were preferentially colocalized within adventitial fibroblasts in HHcy plus angiotensin II mice, which suggested the importance of adventitial fibroblasts activation in Hcy-aggravated AAA. Hcy sequentially stimulated adventitial fibroblasts transformation into myofibroblasts, secretion of interleukin-6 and monocyte chemoattractant protein-1, and consequent recruitment of monocytes/macrophages to adventitial fibroblasts, which was abolished by the NADPH oxidase inhibitor diphenyliodonium. NADPH oxidase 4, but not other homologs of NADPH oxidase, was significantly upregulated by Hcy in adventitial fibroblasts, whereas NADPH oxidase 4 small interfering RNA silencing diminished Hcy-induced adventitial fibroblasts activation. Finally, folic acid supplement (0.071 mu g/g per day) markedly reduced HHcy-aggravated angiotensin II-induced AAA formation in apolipoprotein E-deficient mice.

Conclusions: HHcy may aggravate AAA formation at least partially via activating adventitial fibroblast NADPH oxidase 4. (Circ Res. 2012;111:1261-1273.)

语种: 英语
所属项目编号: 2011 CB503904 ; 2012CB518002 ; 81070243 ; 30870993 ; 30730042 ; 81121061 ; B07001
项目资助者: National Program on Key Basic Research Project (973 Program) ; National Natural Science Foundation of the P. R. China ; 111 Project of Chinese Ministry of Education
WOS记录号: WOS:000310501300008
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67393
Appears in Collections:基础医学院_生理学与病理生理学系_期刊论文

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作者单位: 1.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing, Peoples R China
2.Peking Univ, Dept Physiol & Pathophysiol, Basic Med Coll, Sch Basic Med Sci, Beijing 100191, Peoples R China
3.Capital Med Univ, Beijing Anzhen Hosp, Dept Vasc Surg, Beijing, Peoples R China
4.China Japan Friendship Hosp, Dept Cardiol, Beijing, Peoples R China
5.Peking Univ, Dept Epidemiol & Biostat, Sch Publ Hlth, Beijing 100191, Peoples R China
6.Kings Coll London BHF Ctr, Div Cardiovasc, London, England

Recommended Citation:
Liu, Ziyi,Luo, Hongzhi,Zhang, Lu,et al. Hyperhomocysteinemia Exaggerates Adventitial Inflammation and Angiotensin II-Induced Abdominal Aortic Aneurysm in Mice[J]. CIRCULATION RESEARCH,2012,111(10):1261-U96.
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