Center for Thrombosis and Hemostasis, University Medical Center Mainz, 55131 Mainz, Germany.
INSERM U1116, DCAC (Acute and Chronic Cardiovascular Deficiency), Université de Lorraine, 54500 Nancy, France.
Int J Mol Sci. 2020 Jul 12;21(14):4916. doi: 10.3390/ijms21144916.
Myeloid cells are crucial for the development of vascular inflammation. Low-density lipoprotein receptor-related protein 8 (LRP8) or Apolipoprotein E receptor 2 (ApoER2), is expressed by macrophages, endothelial cells and platelets and has been implicated in the development of cardiovascular diseases. Our aim was to evaluate the role of LRP8, in particular from immune cells, in the development of vascular inflammation.
LRP8 and LRP8 mice (on B6;129S background) were infused with angiotensin II (AngII, 1 mg/kg/day for 7 to 28 day) using osmotic minipumps. Blood pressure was recorded using tail cuff measurements. Vascular reactivity was assessed in isolated aortic segments. Leukocyte activation and infiltration were assessed by flow cytometry of aortic tissue and intravital videomicroscopy imaging. Histological analysis of aortic sections was conducted using sirius red staining.
AngII infusion worsened endothelial-dependent vascular relaxation and immune cells rolling and adherence to the carotid artery in both LRP8 as well as LRP8 mice. However, only LRP8 mice demonstrated a drastically increased mortality rate in response to AngII due to aortic dissection. Bone marrow transplantation revealed that chimeras with LRP8 deficient myeloid cells phenocopied LRP8 mice.
AngII-infused LRP8 deficient mice could be a useful animal model to study aortic dissection reflecting the lethality of this disease in humans.
髓样细胞对于血管炎症的发展至关重要。载脂蛋白 E 受体 2（ApoER2）或 LDL 受体相关蛋白 8（LRP8）在巨噬细胞、内皮细胞和血小板中表达，并与心血管疾病的发展有关。我们的目的是评估 LRP8，特别是来自免疫细胞的 LRP8，在血管炎症发展中的作用。
使用渗透微型泵将 LRP8 和 LRP8 小鼠（B6；129S 背景）输注血管紧张素 II（AngII，每天 1mg/kg，持续 7 至 28 天）。使用尾套测量法记录血压。通过分离的主动脉段评估血管反应性。通过主动脉组织的流式细胞术和活体视频显微镜成像评估白细胞的激活和浸润。使用天狼猩红染色对主动脉切片进行组织学分析。
AngII 输注恶化了内皮依赖性血管舒张以及 LRP8 和 LRP8 小鼠颈动脉中免疫细胞的滚动和黏附。然而，只有 LRP8 小鼠由于主动脉夹层而对 AngII 反应表现出明显增加的死亡率。骨髓移植表明，缺乏 LRP8 髓样细胞的嵌合体模拟了 LRP8 小鼠。
AngII 输注的 LRP8 缺陷型小鼠可能是研究反映人类该疾病致死率的主动脉夹层的有用动物模型。
