Modulation of smooth muscle cell migration by members of the low-density lipoprotein receptor family.
Modulation of smooth muscle cell migration by members of the low-density lipoprotein receptor family.
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DOI：
10.1161/01.atv.0000219692.78477.17
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发表时间：
2006-06
期刊：
影响因子：
--
通讯作者：
H. Bujo;Y. Saito
中科院分区：
文献类型：
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作者：
H. Bujo;Y. Saito
低密度脂蛋白受体家族成员(LRs)在多种组织中除了参与脂蛋白代谢外，还在许多膜相关蛋白的分解代谢中发挥关键作用，如蛋白酶与其受体之间的复合体。最近使用受体缺陷或过度表达的动物和细胞的研究表明，某些受体是血管平滑肌细胞(SMCs)迁移(和增殖)的重要调节因子。在动脉粥样硬化病变形成过程中，动脉内膜或中膜SMC显著诱导LR的表达。由于LRs可以调节尿激酶型纤溶酶原激活物(UPA)受体的活性，可能还可以调节血小板衍生生长因子(PDGF)受体的活性，因此LRs可能通过调节这些膜受体的功能来影响SMC的迁移。因此，SMC的迁移可能受LRs的时间限制性表达的调控。与LRs和膜信号受体之间功能相互作用的概念一致，已发现uPA受体蛋白分解代谢的负调控因子LR11。他汀类药物通过LR11/uPA受体级联调控PDGF诱导的血管内膜细胞迁移。选择性地修饰SMC的LRs/uPA受体/PDGF受体系统对于抑制动脉粥样硬化斑块的形成以及防止血管成形术后内膜增厚具有重要意义。
Low-density lipoprotein receptor family members (LRs) play a key role in the catabolism of many membrane-associated proteins, such as complexes between proteinases and their receptors, in addition to being involved in lipoprotein metabolism as suspected by the hitherto well-established functions of low-density lipoprotein receptor, in a variety of tissues. Recent studies using receptor-deficient or -overexpressing animals and cells have suggested that certain LRs are important regulators of the migration (and proliferation) of vascular smooth muscle cells (SMCs). LR expression is markedly induced in intimal or medial SMCs during the formation of atherosclerotic lesions. Because LRs can modulate the activity of the urokinase-type plasminogen activator (uPA) receptor and possibly of the platelet-derived growth factor (PDGF) receptor, LRs may influence the migration of SMCs through functional modulation of these membrane receptors. Therefore, SMC migration may be regulated by time-restricted expression of LRs. In agreement with the concept of functional interaction between LRs and membrane signaling receptors, a negative regulator of uPA receptor protein catabolism, LR11, has been identified. Statins modulate the PDGF-induced migration of intimal SMCs via the LR11/uPA receptor cascade. Selective modification of the LRs/uPA receptor/PDGF receptor systems in SMCs may be important for suppression of atherosclerotic plaque formation as well as for preventing intimal thickening after angioplasty.