The risk of cardiovascular events rises after AKI. Leukocytes promote atherosclerotic plaque growth and instability. We established a model of enhanced remote atherosclerosis after renal ischemia-reperfusion (IR) injury and investigated the underlying inflammatory mechanisms.

Atherosclerotic lesions and inflammation were investigated in native and bone marrow–transplanted LDL receptor–deficient (LDLr^–/–) mice after unilateral renal IR injury using histology, flow cytometry, and gene expression analysis.

Aortic root atherosclerotic lesions were significantly larger after renal IR injury than in controls. A gene expression screen revealed enrichment for chemokines and their cognate receptors in aortas of IR-injured mice in early atherosclerosis, and of T cell–associated genes in advanced disease. Confocal microscopy revealed increased aortic macrophage proximity to T cells. Differential aortic inflammatory gene regulation in IR-injured mice largely paralleled the pattern in the injured kidney. Single-cell analysis identified renal cell types that produced soluble mediators upregulated in the atherosclerotic aorta. The analysis revealed a marked early increase in Ccl2, which CCR2⁺ myeloid cells mainly expressed. CCR2 mediated myeloid cell homing to the post-ischemic kidney in a cell-individual manner. Reconstitution with Ccr2^–/– bone marrow dampened renal post-ischemic inflammation, reduced aortic Ccl2 and inflammatory macrophage marker CD11c, and abrogated excess aortic atherosclerotic plaque formation after renal IR.

Our data introduce an experimental model of remote proatherogenic effects of renal IR and delineate myeloid CCR2 signaling as a mechanistic requirement. Monocytes should be considered as mobile mediators when addressing systemic vascular sequelae of kidney injury.

AKI 后心血管事件的风险增加。白细胞促进动脉粥样硬化斑块的生长和不稳定。我们建立了肾缺血再灌注（IR）损伤后增强的远端动脉粥样硬化模型，并研究了潜在的炎症机制。

使用组织学、流式细胞术和基因表达分析，研究单侧肾 IR 损伤后的天然小鼠和骨髓移植 LDL 受体缺陷 ( LDLr ^–/– ) 小鼠的动脉粥样硬化病变和炎症。

肾IR损伤后主动脉根部动脉粥样硬化病变明显大于对照组。基因表达筛选揭示了早期动脉粥样硬化中IR损伤小鼠主动脉中趋化因子及其同源受体的富集，以及晚期疾病中T细胞相关基因的富集。共聚焦显微镜显示主动脉巨噬细胞与 T 细胞的接近程度增加。IR损伤小鼠的主动脉炎症基因调节差异在很大程度上与受损肾脏的模式相似。单细胞分析确定了在动脉粥样硬化主动脉中产生上调的可溶性介质的肾细胞类型。分析显示，Ccl2早期显着增加，CCR2 ⁺骨髓细胞主要表达 Ccl2。CCR2 介导骨髓细胞以细胞个体的方式归巢至缺血后的肾脏。用Ccr2 ^–/–骨髓重建可抑制肾脏缺血后炎症，减少主动脉Ccl2和炎症巨噬细胞标记物 CD11c，并消除肾 IR 后过多的主动脉粥样硬化斑块形成。

我们的数据介绍了肾 IR 远程促动脉粥样硬化效应的实验模型，并将骨髓 CCR2 信号传导描述为机械要求。在解决肾损伤的全身血管后遗症时，单核细胞应被视为移动介质。