B cell-derived anti-beta 2 glycoprotein I antibody contributes to hyperhomocysteinemia-aggravated abdominal aortic aneurysm.
B cell-derived anti-beta 2 glycoprotein I antibody contributes to hyperhomocysteinemia-aggravated abdominal aortic aneurysm.
复制标题
B 细胞衍生的抗 β2 糖蛋白 I 抗体导致高同型半胱氨酸血症加重的腹主动脉瘤。
DOI：
10.1093/cvr/cvz288
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发表时间：
2019-11
影响因子：
10.8
通讯作者：
Wang Xian
中科院分区：
文献类型：
--
作者：
Shao Fangyu;Miao Yutong;Zhang Yan;Han Lulu;Ma Xiaolong;Deng Jiacheng;Jiang Changtao;Kong Wei;Xu Qingbo;Feng Juan;Wang Xian
目的：过度活化的B细胞会分泌致病性抗体，进而加速腹主动脉瘤（AAA）的形成。高同型半胱氨酸血症（HHcy）会加剧小鼠腹主动脉瘤的发展；然而，其潜在机制在很大程度上仍不明确。在本（研究中……，这里原文似乎不完整，推测后面还有内容 ）
AIMS
Overactivated B cells secrete pathological antibodies, which in turn accelerate the formation of abdominal aortic aneurysms (AAAs). Hyperhomocysteinemia (HHcy) aggravates AAA in mice; however, the underlying mechanisms remain largely elusive. In this study, we further investigated whether homocysteine (Hcy)-activated B cells produce antigen-specific antibodies that ultimately contribute to AAA formation.
METHODS AND RESULTS
ELISA assays showed that HHcy induced the secretion of anti-beta 2 glycoprotein I (anti-β2GPI) antibody from B cells both in vitro and in vivo. Mechanistically, Hcy increased the accumulation of various lipid metabolites in B cells tested by LC-MS/MS, which contributed to elevated anti-β2GPI IgG secretion. By using the Toll-like receptor 4 (TLR4)-specific inhibitor TAK-242 or TLR4-deficient macrophages, we found that culture supernatants from Hcy-activated B cells and HHcy plasma IgG polarized inflammatory macrophages in a TLR4-dependent manner. In addition, HHcy markedly increased the incidence of elastase- and CaPO4-induced AAA in male BALB/c mice, which was prevented in μMT mice. To further determine the importance of IgG in HHcy-aggravated AAA formation, we purified plasma IgG from HHcy or control mice and then transferred the IgG into μMT mice, which were subsequently subjected to elastase- or CaPO4-induced AAA. Compared with μMT mice that received plasma IgG from control mice, μMT mice that received HHcy plasma IgG developed significantly exacerbated elastase- or CaPO4-induced AAA accompanied by increased elastin degradation, MMP2/9 expression, and anti-β2GPI IgG deposition in vascular lesions, as shown by immunofluorescence histochemical staining.
CONCLUSION
Our findings reveal a novel mechanism by which Hcy-induced B cell-derived pathogenic anti-β2GPI IgG might, at least in part, contribute to HHcy-aggravated chronic vascular inflammation and AAA formation.
TRANSLATIONAL PERSPECTIVE
HHcy is an independent risk factor for cardiovascular diseases in which B cell secretion of IgG antibodies play a key role. However, whether the antigen specific antibody production is changed during HHcy-accelerated AAA remains unclear. Our results provided the first evidence supporting the important role of activated B cell-derived anti-β2GPI IgG in HHcy-aggravated chronic vascular inflammation and AAA formation. It sheds new light on understanding pathogenesis of HHcy-accelerated AAA. In addition, anti-β2GPI IgG may be a potential diagnostic marker and therapeutic target for HHcy-related vascular injury.
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影响因子：
5
作者：
Mineo, Chieko
通讯作者：
Mineo, Chieko
DOI：
10.1161/atvbaha.116.307559
发表时间：
2016-11
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Schaheen B;Downs EA;Serbulea V;Almenara CC;Spinosa M;Su G;Zhao Y;Srikakulapu P;Butts C;McNamara CA;Leitinger N;Upchurch GR Jr;Meher AK;Ailawadi G
通讯作者：
Ailawadi G
DOI：
10.1056/nejm199711273372215
发表时间：
2000
期刊：
--
影响因子：
--
作者：
An;Rik;Ordrehaug;Elga;Efsum;tein;Mil;Ollset
通讯作者：
An;Rik;Ordrehaug;Elga;Efsum;tein;Mil;Ollset
DOI：
10.1016/j.ejvs.2003.09.001
发表时间：
2004
期刊：
European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery
影响因子：
--
作者：
A. Warsi;Bruce Davies;G. Morris-Stiff;D. Hullin;Michael H Lewis
通讯作者：
A. Warsi;Bruce Davies;G. Morris-Stiff;D. Hullin;Michael H Lewis
DOI：
10.1016/j.ajpath.2014.07.006
发表时间：
2014-11
期刊：
The American journal of pathology
影响因子：
--
作者：
Akshaya K. Meher;W. F. Johnston;G. Lu;Nicolas H. Pope;C. Bhamidipati;Daniel Harmon;Gang Su;Yunge Zhao;C. McNamara;G. Upchurch;G. Ailawadi
通讯作者：
Akshaya K. Meher;W. F. Johnston;G. Lu;Nicolas H. Pope;C. Bhamidipati;Daniel Harmon;Gang Su;Yunge Zhao;C. McNamara;G. Upchurch;G. Ailawadi