Boucher Philippe, Gotthardt Michael, Li Wei-Ping, Anderson Richard G W, Herz Joachim
Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9046, USA.
Science. 2003 Apr 11;300(5617):329-32. doi: 10.1126/science.1082095.
Vascular smooth muscle cell (SMC) proliferation and migration are important events in the development of atherosclerosis. The low-density lipoprotein receptor-related protein (LRP1) mediates suppression of SMC migration induced by platelet-derived growth factor (PDGF). Here we show that LRP1 forms a complex with the PDGF receptor (PDGFR). Inactivation of LRP1 in vascular SMCs of mice causes PDGFR overexpression and abnormal activation of PDGFR signaling, resulting in disruption of the elastic layer, SMC proliferation, aneurysm formation, and marked susceptibility to cholesterol-induced atherosclerosis. The development of these abnormalities was reduced by treatment with Gleevec, an inhibitor of PDGF signaling. Thus, LRP1 has a pivotal role in protecting vascular wall integrity and preventing atherosclerosis by controlling PDGFR activation.
血管平滑肌细胞（SMC）的增殖和迁移是动脉粥样硬化发展过程中的重要事件。低密度脂蛋白受体相关蛋白（LRP1）介导对血小板衍生生长因子（PDGF）诱导的SMC迁移的抑制作用。在此我们表明，LRP1与PDGF受体（PDGFR）形成复合物。小鼠血管平滑肌细胞中LRP1的失活导致PDGFR过表达和PDGFR信号的异常激活，从而导致弹性层破坏、SMC增殖、动脉瘤形成以及对胆固醇诱导的动脉粥样硬化的显著易感性。用PDGF信号抑制剂格列卫治疗可减少这些异常情况的发生。因此，LRP1在通过控制PDGFR激活来保护血管壁完整性和预防动脉粥样硬化方面具有关键作用。
