Aging leads to a proinflammatory state within the vasculature without disease, yet whether this inflammatory state occurs during atherogenesis remains unclear. Here, we examined how aging impacts atherosclerosis using Ldlr^−/− mice, an established murine model of atherosclerosis. We found that aged atherosclerotic Ldlr^−/− mice exhibited enhanced atherogenesis within the aorta. Aging also led to increased LDL levels, elevated blood pressure on a low‐fat diet, and insulin resistance after a high‐fat diet (HFD). On a HFD, aging increased a monocytosis in the peripheral blood and enhanced macrophage accumulation within the aorta. When we conducted bone marrow transplant experiments, we found that stromal factors contributed to age‐enhanced atherosclerosis. To delineate these stromal factors, we determined that the vasculature exhibited an age‐enhanced inflammatory response consisting of elevated production of CCL‐2, osteopontin, and IL‐6 during atherogenesis. In addition, in vitro cultures showed that aging enhanced the production of osteopontin by vascular smooth muscle cells. Functionally, aged atherosclerotic aortas displayed higher monocyte chemotaxis than young aortas. Hence, our study has revealed that aging induces metabolic dysfunction and enhances vascular inflammation to promote a peripheral monocytosis and macrophage accumulation within the atherosclerotic aorta.

中文翻译：

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与年龄相关的血管炎症在动脉粥样硬化形成过程中促进单核细胞增多。

衰老导致脉管系统内的促炎状态而没有疾病，但是尚不清楚该炎性状态是否在动脉粥样硬化形成期间发生。在这里，我们使用Ldlr ^-/-小鼠（一种已建立的鼠科动物动脉粥样硬化模型）研究了衰老如何影响动脉粥样硬化。我们发现老年动脉粥样硬化Ldlr ^-/-小鼠表现出增强的主动脉内动脉粥样硬化。衰老还导致LDL水平升高，低脂饮食导致血压升高以及高脂饮食（HFD）后的胰岛素抵抗。在HFD上，衰老会增加外周血中的单核细胞增多，并增强主动脉内巨噬细胞的积累。当我们进行骨髓移植实验时，我们发现基质因素导致了年龄增加的动脉粥样硬化。为了描述这些基质因素，我们确定脉管系统显示出年龄增强的炎症反应，包括在动脉粥样硬化发生期间CCL-2，骨桥蛋白和IL-6的产生增加。另外，体外培养表明，衰老增强了血管平滑肌细胞产生骨桥蛋白的能力。从功能上讲，老年动脉粥样硬化主动脉显示出比年轻主动脉更高的单核细胞趋化性。因此，我们的研究表明，衰老会诱发代谢功能障碍，并增强血管炎症，从而促进动脉粥样硬化主动脉内的外周单核细胞增多和巨噬细胞积累。