CXCL1: a novel therapeutic target to increase aneurysm healing after coil embolization.

OBJECTIVE: CXCL1 is highly expressed in human aneurysms but its role in aneurysm healing is unknown. The objective of this study was to determine whether CXCL1 neutralization increases murine aneurysm healing post-coiling. METHODS: Carotid artery aneurysms were created in female and male C57BL/6 mice. CXCL1 expression was compared between aneurysms and sham-operated carotid arteries. In a separate cohort, aneurysms were coiled with poly (lactic-co-glycolic acid) (PLGA)-coated coils. Mice received intraperitoneal injections of either CXCL1 neutralizing antibody or IgG control for 7, 14, or 21 days post-coiling. Coiled aneurysms were assessed for aneurysm healing, neutrophil infiltration, macrophage polarization, and total macrophage burden. RESULTS: CXCL1 is highly expressed in murine carotid artery aneurysms. CXCL1 neutralization significantly increased aneurysm healing compared to IgG when administered for 14 days (females: 66.4% vs. 51.2%, p = 0.03; males: 69.8% vs. 47.0%, p = 0.004) and 21 days (females: 71.9% vs. 44.3%, p = 0.002; males: 67.8% vs. 61.6%, p = 0.02), but not when given for only 7 days (females: 48.1% vs. 49.4%; males: 52.3% vs. 50.4%). 14 days of CXCL1 neutralization decreased neutrophil infiltration (females: 0.43 vs. 5.21 cells/high power field (hpf), p = 0.04; males: 0.00 vs. 4.42 cells/hpf, p = 0.04) and increased reparative M2 macrophages (females: 2.25 vs. 0.79 cells/hpf, p = 0.03; males: 2.00 vs. 0.27 cells/hpf, p = 0.02). CONCLUSIONS: CXCL1 neutralization for 14 or 21 days improved aneurysm healing in female and male mice. 14 days of CXCL1 neutralization decreased neutrophil infiltration and increased M2 macrophage polarization. Systemic CXCL1 neutralization is a promising potential therapy to improve aneurysm healing by modulating the inflammatory response after coiling.