The G534E polymorphism of the gene encoding the factor VII-activating protease is associated with cardiovascular risk due to increased neointima formation.
The G534E polymorphism of the gene encoding the factor VII-activating protease is associated with cardiovascular risk due to increased neointima formation.
复制标题
DOI：
10.1084/jem.20052546
复制
发表时间：
2006-12-25
期刊：
影响因子：
--
通讯作者：
Kanse SM
中科院分区：
文献类型：
--
作者：
Sedding D;Daniel JM;Muhl L;Hersemeyer K;Brunsch H;Kemkes-Matthes B;Braun-Dullaeus RC;Tillmanns H;Weimer T;Preissner KT;Kanse SM
因子7活化蛋白酶（FSAP） G534E多态性（Marburg I [MI]）与颈动脉狭窄和心血管疾病相关。我们之前已经证明FSAP存在于动脉粥样硬化斑块中，它是体外血管平滑肌增殖和迁移的有效抑制剂。研究了野生型（WT）和MI-FSAP对小鼠股动脉钢丝损伤后新生内膜形成的影响。局部应用WT-FSAP导致新内膜形成减少70%，这种效果依赖于FSAP的蛋白酶活性。MI-FSAP在体内没有抑制新生内膜的形成。这是由于与WT-FSAP相比，MI-FSAP对血小板衍生生长因子BB（新内膜发展的关键介质）的蛋白水解活性降低。MI-FSAP无法抑制血管平滑肌积累，这解释了mi多态性与心血管风险增加之间的联系。因此，FSAP在血管中具有保护功能，分析心肌梗死多态性可能与再狭窄的临床相关。
The G534E polymorphism (Marburg I [MI]) of factor VII–activating protease (FSAP) is associated with carotid stenosis and cardiovascular disease. We have previously demonstrated that FSAP is present in atherosclerotic plaques and it is a potent inhibitor of vascular smooth muscle proliferation and migration in vitro. The effect of wild-type (WT)- and MI-FSAP on neointima formation in the mouse femoral artery after wire-induced injury was investigated. Local application of WT-FSAP led to a 70% reduction in the neointima formation, and this effect was dependent on the protease activity of FSAP. MI-FSAP did not inhibit neointima formation in vivo. This is due to a reduced proteolytic activity of MI-FSAP, compared to WT-FSAP, toward platelet-derived growth factor BB, a key mediator of neointima development. The inability of MI-FSAP to inhibit vascular smooth muscle accumulation explains the observed linkage between the MI-polymorphism and increased cardiovascular risk. Hence, FSAP has a protective function in the vasculature, and analysis of MI polymorphism is likely to be clinically relevant in restenosis.
登录
查看更多内容
影响因子：
20.3
作者：
Hoppe, B;Tolou, F;Salama, A
通讯作者：
Salama, A
影响因子：
4.1
作者：
Nakazawa, F;Kannemeier, C;Preissner, KT
通讯作者：
Preissner, KT
影响因子：
1.1
作者：
Roemisch, J;Feussner, A;Weimer, T
通讯作者：
Weimer, T
影响因子：
6.7
作者：
Ireland, H;Miller, GJ;Humphries, SE
通讯作者：
Humphries, SE
影响因子：
5
作者：
Sata, M;Maejima, Y;Nagai, R
通讯作者：
Nagai, R