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.

动脉粥样硬化是脉管系统的慢性炎性疾病，由胆固醇沉积到动脉壁中引发，触发了免疫和炎性细胞（包括单核细胞和巨噬细胞）的浸润。随着动脉粥样硬化斑块的进展，局部缺氧促进血管脉管的代偿性血管生成。未成熟的新血管易于渗漏，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鉴定出具有不同表型的巨噬细胞，其范围从经典的炎性亚型到交替激活的抗炎性巨噬细胞。抗炎症性的清除血红蛋白的CD163 +巨噬细胞存在于富含新生血管和出血的区域。然而，这些巨噬细胞在动脉粥样硬化中的作用尚不清楚。Guo，Akahori和同事在本期JCI中显示，CD163 +巨噬细胞通过涉及血红蛋白的一种机制来促进人和小鼠动脉粥样硬化病变中的血管生成，血管通透性和白细胞浸润：触珠蛋白/ CD163 /HIF1α介导的VEGF诱导。因此，这项研究确定了CD163 +巨噬细胞的促动脉粥样硬化特性，以前认为这是有益的。