Angiotensin II-accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice.
Angiotensin II-accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice.
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在骨桥蛋白缺陷小鼠中，血管紧张素 II 加速的动脉粥样硬化和动脉瘤形成被减弱。
DOI：
10.1172/jci18141
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Hsueh,WillaA
中科院分区：
文献类型：
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作者：
Bruemmer,Dennis;Collins,AlanR;Noh,Grace;Wang,Wei;Territo,Mary;Arias-Magallona,Sarah;Fishbein,MichaelC;Blaschke,Florian;Kintscher,Ulrich;Graf,Kristof;Law,RonaldE;Hsueh,WillaA
骨桥蛋白（OPN）在动脉粥样硬化病变中表达，特别是在糖尿病患者中。为了确定OPN在动脉粥样硬化形成中的作用，ApoE-/-OPN+/+、ApoE-/-OPN+/-和ApoE-/-OPN-/-小鼠被输注Ang II，诱导血管OPN表达并加速动脉粥样硬化。与ApoE-/-OPN+/+小鼠相比，ApoE-/-OPN+/-和ApoE-/-OPN-/-小鼠发生较少的Ang II加速的动脉粥样硬化。与接受ApoE-/-OPN+/+细胞的动物相比，移植ApoE-/-OPN-/-小鼠骨髓的ApoE-/-小鼠发生较少的Ang II诱导的动脉粥样硬化。血管紧张素II输注ApoE-/-OPN-/-小鼠的主动脉表达较少的CD 68、C-C-趋化因子受体2和VCAM-1。腹腔注射巯基乙酸盐后，OPN-/-小鼠白细胞的募集受损，OPN-/-小鼠白细胞的基础迁移和MCP-1介导的迁移减少。此外，血管紧张素II输注ApoE-/-OPN-/-小鼠动脉粥样硬化病变中的巨噬细胞活力降低。最后，Ang II诱导的ApoE-/-OPN-/-小鼠腹主动脉瘤形成减少，并与MMP-2和MMP-9活性降低相关。这些数据表明白细胞来源的OPN在介导Ang II加速的动脉粥样硬化和动脉瘤形成中起重要作用。
Osteopontin (OPN) is expressed in atherosclerotic lesions, particularly in diabetic patients. To determine the role of OPN in atherogenesis,ApoE–/–OPN+/+,ApoE–/–OPN+/–, andApoE–/–OPN–/–mice were infused with Ang II, inducing vascular OPN expression and accelerating atherosclerosis. Compared withApoE–/–OPN+/+mice,ApoE–/–OPN+/–andApoE–/–OPN–/–mice developed less Ang II–accelerated atherosclerosis.ApoE–/–mice transplanted with bone marrow derived fromApoE–/–OPN–/–mice had less Ang II–induced atherosclerosis compared with animals receivingApoE–/–OPN+/+cells. Aortae from Ang II–infusedApoE–/–OPN–/–mice expressed less CD68, C-C-chemokine receptor 2, and VCAM-1. In response to intraperitoneal thioglycollate, recruitment of leukocytes inOPN–/–mice was impaired, andOPN–/–leukocytes exhibited decreased basal and MCP-1–directed migration. Furthermore, macrophage viability in atherosclerotic lesions from Ang II–infusedApoE–/–OPN–/–mice was decreased. Finally, Ang II–induced abdominal aortic aneurysm formation inApoE–/–OPN–/–mice was reduced and associated with decreased MMP-2 and MMP-9 activity. These data suggest an important role for leukocyte-derived OPN in mediating Ang II–accelerated atherosclerosis and aneurysm formation.