Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Department of Pathology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Am J Physiol Heart Circ Physiol. 2020 May 1;318(5):H1068-H1079. doi: 10.1152/ajpheart.00690.2019. Epub 2020 Mar 27.
The clinical risks and prognosis of diabetic vascular intimal calcification (VIC) and medial calcification (VMC) are different. This study aims to investigate the mechanism of VIC/VMC translocation. Anterior tibial arteries were collected from patients with diabetic foot amputation. The patients were then divided into VIC and VMC groups. There were plaques in all anterior tibial arteries, while the enrichment of galectin-3 in arterial plaques in the VIC group was significantly higher than that in the VMC group. Furthermore, a macrophage/vascular smooth muscle cell (VSMC) coculture system was constructed. VSMC-derived extracellular vesicles (EVs) was labeled with fluorescent probe. After macrophages were pretreated with recombinant galectin-3 protein, the migration of VSMC-derived EVs and VSMC-derived calcification was more pronounced. And anti-galectin-3 antibody can inhibit this process of EVs and calcification translocation. Then, lentivirus (LV)-treated bone marrow cells (BMCs) were transplanted into apolipoprotein E-deficient (ApoE) mice, and a diabetic atherosclerosis mouse model was constructed. After 15 wk of high-fat diet, ApoE mice transplanted with LV-shgalectin-3 BMCs exhibited medial calcification and a concentrated distribution of EVs in the media. In conclusion, upregulation of galectin-3 in macrophages promotes the migration of VSMC-derived EVs to the intima and induces diabetic vascular intimal calcification. The clinical risk and prognosis of vascular intimal and medial calcification are different. Macrophage galectin-3 regulates the migration of vascular smooth muscle cell-derived extracellular vesicles and mediates diabetic vascular intimal/medial calcification translocation. This study may provide insights into the early intervention in diabetic vascular calcification.
糖尿病血管内膜钙化（VIC）和中膜钙化（VMC）的临床风险和预后不同。本研究旨在探讨 VIC/VMC 易位的机制。从糖尿病足截肢患者采集胫前动脉。然后将患者分为 VIC 和 VMC 组。所有胫前动脉均有斑块，而 VIC 组动脉斑块中半乳糖凝集素-3 的富集明显高于 VMC 组。此外，构建了巨噬细胞/血管平滑肌细胞（VSMC）共培养系统。用荧光探针标记 VSMC 衍生的细胞外囊泡（EVs）。用重组半乳糖凝集素-3 蛋白预处理巨噬细胞后，VSMC 衍生 EVs 和 VSMC 衍生钙化的迁移更为明显。并且抗半乳糖凝集素-3 抗体可以抑制 EVs 和钙化易位的这个过程。然后，将慢病毒（LV）处理的骨髓细胞（BMCs）移植到载脂蛋白 E 缺陷（ApoE）小鼠中，构建糖尿病动脉粥样硬化小鼠模型。在高脂肪饮食 15 周后，移植了 LV-shgalectin-3 BMCs 的 ApoE 小鼠表现出中膜钙化和 EVs 在中膜中的集中分布。总之，巨噬细胞中半乳糖凝集素-3 的上调促进了 VSMC 衍生 EVs 向内膜的迁移，并诱导了糖尿病血管内膜钙化。血管内膜和中膜钙化的临床风险和预后不同。巨噬细胞半乳糖凝集素-3 调节血管平滑肌细胞衍生的细胞外囊泡的迁移，并介导糖尿病血管内膜/中膜钙化易位。这项研究可能为糖尿病血管钙化的早期干预提供思路。
