J Clin Invest. 2018 Mar 1;128(3):910-912. doi: 10.1172/JCI120123. Epub 2018 Feb 19.
Atherosclerosis is a chronic inflammatory disease of the vasculature that is initiated by cholesterol deposition into the arterial wall, which triggers the infiltration of immune and inflammatory cells, including monocytes and macrophages. As atherosclerotic plaques progress, localized hypoxia promotes compensatory angiogenesis from the vasa vasorum. Immature neovessels are prone to leakage, thus destabilizing the plaque and leading to intraplaque hemorrhage. Macrophages with different phenotypes, ranging from classical inflammatory subtypes to alternatively activated antiinflammatory macrophages, have been identified in atherosclerotic lesions. Antiinflammatory hemoglobin-scavenging CD163+ macrophages are present in neovessel- and hemorrhage-rich areas; however, the role of these macrophages in atherogenesis has been unclear. In this issue of the JCI, Guo, Akahori, and colleagues show that CD163+ macrophages promote angiogenesis, vessel permeability, and leucocyte infiltration in human and mouse atherosclerotic lesions through a mechanism involving hemoglobin:haptoglobin/CD163/HIF1α-mediated VEGF induction. This study thus identifies proatherogenic properties of CD163+ macrophages, which previously were thought to be beneficial.
动脉粥样硬化是一种慢性血管炎症性疾病，由胆固醇在动脉壁内沉积引发，进而触发免疫细胞和炎症细胞（包括单核细胞和巨噬细胞）浸润。随着动脉粥样硬化斑块的进展，局部缺氧会促进从血管丛中发生代偿性血管生成。不成熟的新生血管容易发生渗漏，从而使斑块不稳定并导致斑块内出血。在动脉粥样硬化病变中已经鉴定出具有不同表型的巨噬细胞，从经典炎症亚型到替代性激活的抗炎巨噬细胞。富含新生血管和出血的区域存在抗炎性血红蛋白清除 CD163+巨噬细胞；然而，这些巨噬细胞在动脉粥样硬化形成中的作用尚不清楚。在本期 JCI 中，Guo、Akahori 及其同事表明，CD163+巨噬细胞通过血红蛋白：触珠蛋白/CD163/HIF1α 介导的 VEGF 诱导，在人类和小鼠动脉粥样硬化病变中促进血管生成、血管通透性和白细胞浸润。因此，这项研究确定了 CD163+巨噬细胞的促动脉粥样硬化特性，此前人们认为这些特性是有益的。
