Department of Cardiology, Shanghai East Hospital, Tongji University, Jimo Road 150, Shanghai, 200120, China.
Hum Genet. 2020 Apr;139(4):447-459. doi: 10.1007/s00439-020-02124-8. Epub 2020 Feb 19.
Low-density lipoprotein receptor-related protein 6 (LRP6) is a member of the low-density lipoprotein receptors (LDLRs) family and accumulating evidence points to the critical role of LRP6 in cardiovascular health and homeostasis. In addition to presenting the well-appreciated roles in canonical signaling regulating blood pressure, blood glucose, lipid metabolism, atherosclerosis, cardiac valve disease, cardiac development, Alzheimer's disease and tumorigenesis, LRP6 also inhibits non-canonical Wnt signals that promote arterial smooth muscle cell proliferation and vascular calcification. Noticeably, the role of LRP6 is displayed in cardiometabolic disease, an increasingly important clinical burden with aging and obesity. The prospect for cardiovascular diseases treatment via targeting LRP6-mediated signaling pathways may improve central blood pressure and lipid metabolism, and reduce neointima formation and myocardial ischemia-reperfusion injury. Thus, a deep and comprehensive understanding of LRP6 structure, function and signaling pathways will contribute to clinical diagnosis, therapy and new drug development for LRP6-related cardiovascular diseases.
低密度脂蛋白受体相关蛋白 6（LRP6）是低密度脂蛋白受体（LDLRs）家族的成员，越来越多的证据表明 LRP6 在心血管健康和稳态中起着关键作用。除了在调节血压、血糖、脂质代谢、动脉粥样硬化、心脏瓣膜疾病、心脏发育、阿尔茨海默病和肿瘤发生的经典信号中具有明显作用外，LRP6 还抑制促进动脉平滑肌细胞增殖和血管钙化的非经典 Wnt 信号。值得注意的是，LRP6 在代谢性心血管疾病中发挥作用，随着老龄化和肥胖，这种疾病的临床负担日益加重。通过靶向 LRP6 介导的信号通路治疗心血管疾病的前景可能会改善中心血压和脂质代谢，减少新生内膜形成和心肌缺血再灌注损伤。因此，深入全面地了解 LRP6 的结构、功能和信号通路将有助于 LRP6 相关心血管疾病的临床诊断、治疗和新药开发。
