Inflammatory mediators such as cytokines and chemokines are crucially involved in the development of abdominal aortic aneurysm (AAA). Here we report that CaCl₂ application into abdominal aorta induces AAA with intra-aortic infiltration of macrophages as well as enhanced expression of chemokine (C-C motif) ligand 3 (CCL3) and MMP-9. Moreover, infiltrating macrophages express C-C chemokine receptor 5 (CCR5, a specific receptor for CCL3) and MMP-9. Both Ccl3^−/− mice and Ccr5^−/− but not Ccr1^−/− mice exhibit exaggerated CaCl₂-inducced AAA with augmented macrophage infiltration and MMP-9 expression. Similar observations are also obtained on an angiotensin II-induced AAA model. Immunoneutralization of CCL3 mimics the phenotypes observed in CaCl₂-treated Ccl3^−/− mice. On the contrary, CCL3 treatment attenuates CaCl₂-induced AAA in both wild-type and Ccl3^−/− mice. Consistently, we find that the CCL3–CCR5 axis suppresses PMA-induced enhancement of MMP-9 expression in macrophages. Thus, CCL3 can be effective to prevent the development of CaCl₂-induced AAA by suppressing MMP-9 expression.

炎性介质（例如细胞因子和趋化因子）与腹主动脉瘤（AAA）的发展密切相关。在这里我们报告CaCl ₂应用于腹主动脉诱导AAA与巨噬细胞的主动脉内浸润以及趋化因子（CC主题）配体3（CCL3）和MMP-9的表达增强。此外，浸润的巨噬细胞表达CC趋化因子受体5（CCR5，CCL3的特异性受体）和MMP-9。这两种CCL3 ^{- / -}小鼠和CCR5 ^{- / -}但不是CCR1 ^{- / -}小鼠表现出夸张的氯化钙₂诱导的AAA，具有增强的巨噬细胞浸润和MMP-9表达。在血管紧张素II诱导的AAA模型上也获得了类似的观察结果。CCL3的免疫原化模拟了在用CaCl ₂处理的Ccl3 ^-//小鼠中观察到的表型。相反，CCL3处理在野生型和Ccl3 ^-/-小鼠中均减弱了CaCl ₂诱导的AAA 。一致地，我们发现CCL3–CCR5轴抑制了巨噬细胞中PMA诱导的MMP-9表达的增强。因此，CCL3可通过抑制MMP-9表达来有效防止CaCl ₂诱导的AAA的发展。