Cyclophilin A is an inflammatory mediator that promotes atherosclerosis in apolipoprotein E-deficient mice.
Cyclophilin A is an inflammatory mediator that promotes atherosclerosis in apolipoprotein E-deficient mice.
复制标题
DOI：
10.1084/jem.20101174
复制
发表时间：
2011-01-17
期刊：
影响因子：
--
通讯作者：
Berk BC
中科院分区：
文献类型：
--
作者：
Nigro P;Satoh K;O'Dell MR;Soe NN;Cui Z;Mohan A;Abe J;Alexis JD;Sparks JD;Berk BC
亲环蛋白A促进动脉粥样硬化的部分途径是通过诱导活性氧、促进内皮细胞凋亡和巨噬细胞募集到病变部位。亲环蛋白A （CyPA，由Ppia编码）是一种在炎症刺激下分泌的普遍表达蛋白。CyPA刺激血管平滑肌细胞迁移和增殖、内皮细胞黏附分子表达和炎症细胞趋化。鉴于这些活性，我们假设CyPA会促进动脉粥样硬化。与Apoe - / - Ppia - / -小鼠相比，饲喂高胆固醇饮食16周的载脂蛋白e -缺乏（Apoe - / -）小鼠发生了更严重的动脉粥样硬化。此外，CyPA缺乏与低密度脂蛋白摄取减少、血管细胞粘附分子1 （VCAM-1）表达减少、细胞凋亡和内皮型一氧化氮合酶（eNOS）表达增加有关。为了了解CyPA在动脉粥样硬化发展中的血管作用，进行了骨髓（BM）细胞移植。在用CyPA+/+ BM细胞重建后，Apoe−/−小鼠的动脉粥样硬化比Apoe−/−Ppia−/−小鼠更严重，这表明血管源性CyPA在动脉粥样硬化的进展中起着至关重要的作用。这些数据确定了CyPA在动脉粥样硬化中的作用，并提示CyPA可作为心血管治疗的靶点。
Cyclophilin A promotes atherosclerosis in part by inducing reactive oxygen species and promoting endothelial cell apoptosis and macrophage recruitment into lesions. Cyclophilin A (CyPA; encoded by Ppia) is a ubiquitously expressed protein secreted in response to inflammatory stimuli. CyPA stimulates vascular smooth muscle cell migration and proliferation, endothelial cell adhesion molecule expression, and inflammatory cell chemotaxis. Given these activities, we hypothesized that CyPA would promote atherosclerosis. Apolipoprotein E–deficient (Apoe−/−) mice fed a high-cholesterol diet for 16 wk developed more severe atherosclerosis compared with Apoe−/−Ppia−/− mice. Moreover, CyPA deficiency was associated with decreased low-density lipoprotein uptake, VCAM-1 (vascular cell adhesion molecule 1) expression, apoptosis, and increased eNOS (endothelial nitric oxide synthase) expression. To understand the vascular role of CyPA in atherosclerosis development, bone marrow (BM) cell transplantation was performed. Atherosclerosis was greater in Apoe−/− mice compared with Apoe−/−Ppia−/− mice after reconstitution with CyPA+/+ BM cells, indicating that vascular-derived CyPA plays a crucial role in the progression of atherosclerosis. These data define a role for CyPA in atherosclerosis and suggest CyPA as a target for cardiovascular therapies.
登录
查看更多内容
DOI：
10.1152/ajpendo.2000.279.5.e1003
发表时间：
2000-11-01
影响因子：
5.1
作者：
Chirieac, DV;Chirieac, LR;Sparks, JD
通讯作者：
Sparks, JD
影响因子：
4.4
作者：
Arora, K;Gwinn, WM;Constant, SL
通讯作者：
Constant, SL
影响因子：
32.4
作者：
Colgan, J;Asmal, M;Luban, J
通讯作者：
Luban, J
影响因子：
3.1
作者：
Fernandez-Miranda, C;Guijarro, C;del Palacio, A
通讯作者：
del Palacio, A
影响因子：
20.1
作者：
Atkins GB;Wang Y;Mahabeleshwar GH;Shi H;Gao H;Kawanami D;Natesan V;Lin Z;Simon DI;Jain MK
通讯作者：
Jain MK