Caveolin-1 deficiency decreases atherosclerosis by hampering leukocyte influx into the arterial wall and generating a regulatory T-cell response
Caveolin-1 deficiency decreases atherosclerosis by hampering leukocyte influx into the arterial wall and generating a regulatory T-cell response
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DOI：
10.1096/fj.11-183350
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发表时间：
2011-11-01
期刊：
影响因子：
4.8
通讯作者：
Lutgens, Esther
中科院分区：
文献类型：
--
作者：
Engel, David;Beckers, Linda;Lutgens, Esther
Caveolin-1在动脉粥样硬化中起着至关重要的作用，这主要归因于它对低密度脂蛋白（LDL）转胞吞作用的影响。然而，caveolin-1 也与炎症的调节有关。我们研究了caveolin-1缺陷对动脉粥样硬化的影响及其伴随的斑块和淋巴相关免疫学和炎症的变化。 Cav1(-/-)Apoe(-/-) 小鼠的斑块大小减少了 15 倍，且斑块中巨噬细胞、T 细胞和中性粒细胞较少。活体显微镜检查显示，Cav1(-/-)Apoe(-/-) 小鼠的白细胞对血管壁的粘附减少了 83%，这可能是由于内皮趋化因子配体 2 (CCL-2/MCP-1) 和血管细胞粘附分子 1 (VCAM-1) 表达减少所致。 Caveolin-1缺陷导致淋巴器官中调节性T细胞增加57%，CD4(+)效应T细胞减少4%。骨髓移植显示，接受 Cav1(+/+)Apoe(-/-) 或 Cav1(-/-)Apoe(-/-) 骨髓的 Cav1(-/-)Apoe(-/-) 小鼠的骨髓斑块缩小 4 至 4.5 倍，且没有额外的表型变化。相比之下，接受Cav1(-/-)Apoe(-/-)或Cav1(+/+)Apoe(-/-)骨髓的Cav1(+/+)Apoe(-/-)受体的动脉粥样硬化并未受到影响。然而，Cav1(-/-) Apoe(-/-) 骨髓的存在与抗炎 T 细胞谱相关。我们的研究表明，非造血性 Caveolin-1 决定斑块大小，而造血性 Caveolin-1 则调节淋巴免疫调节。然而，两者都是斑块表型调节所必需的。-Engel, D.、Beckers, L.、Wijnands, E.、Seijkens, T.、Lievens, D.、Drechsler, M.、Gerdes, N.、Soehnlein, O.、Daemen, M. J. A. P.、Stan, R. V.、Biessen, E. A. L.、Lutgens, E. Caveolin-1 缺乏症减少 通过阻碍白细胞流入动脉壁并产生调节性 T 细胞反应来预防动脉粥样硬化。 FASEB J. 25, 3838-3848 (2011)。 www.fasebj.org
Caveolin-1 plays a crucial role in atherosclerosis, which is mainly attributed to its effects on low-density-lipoprotein (LDL) transcytosis. However, caveolin-1 has also been implicated in the regulation of inflammation. We investigated the effects of caveolin-1 deficiency in atherosclerosis with its accompanying changes in plaque- and lymphoid-related immunology and inflammation. Cav1(-/-)Apoe(-/-) mice exhibited a 15-fold reduction in plaque size with plaques containing fewer macrophages, T cells, and neutrophils. Intravital microscopy revealed 83% less leukocyte adhesion to the vessel wall in Cav1(-/-)Apoe(-/-) mice, which could be attributed to reduced endothelial chemokine ligand-2 (CCL-2/MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) expression. Caveolin-1 deficiency resulted in a 57% increase in regulatory T cells and a 4% decrease in CD4(+) effector T cells in lymphoid organs. Bone marrow transplantations revealed that Cav1(-/-)Apoe(-/-) mice receiving Cav1(+/+)Apoe(-/-) or Cav1(-/-)Apoe(-/-) bone marrow presented 4- to 4.5-fold smaller plaques with no additional phenotypic changes. In contrast, atherosclerosis was not affected in Cav1(+/+) Apoe(-/-) recipients receiving Cav1(-/-)Apoe(-/-) or Cav1(+/+) Apoe(-/-) bone marrow. However, the presence of Cav1(-/-) Apoe(-/-) bone marrow was associated with an anti-inflammatory T-cell profile. Our study reveals that nonhematopoietic caveolin-1 determines plaque size, whereas hematopoietic caveolin-1 regulates lymphoid immune-modulation. However, both are required for phenotypic modulation of plaques.-Engel, D., Beckers, L., Wijnands, E., Seijkens, T., Lievens, D., Drechsler, M., Gerdes, N., Soehnlein, O., Daemen, M. J. A. P., Stan, R. V., Biessen, E. A. L., Lutgens, E. Caveolin-1 deficiency decreases atherosclerosis by hampering leukocyte influx into the arterial wall and generating a regulatory T-cell response. FASEB J. 25, 3838-3848 (2011). www.fasebj.org