학술대회 안내 사전등록 안내 초록등록 안내 초록등록/관리 숙박및교통 안내


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Macrophage depletion by clodronate liposomes suppresses neointimal formation after carotid artery injury in Apolipoprotein E-deficient mice
고려대학교 안암병원 심혈관센터¹ 고려대학교 구로병원 심혈관센터² 가천대학교 길병원 심혈관센터³
홍순준¹, 서홍석² 안태훈³ 박창규² 오동주² 나승운² 심완주¹ 손창성¹ 최종일¹ 주형준¹ 신승용¹ 신성희¹ 임도선¹
BACKGROUND: Inflammation plays a key role in the neointimal formation after mechanical vascular injury. Clodronate liposomes deplete phagocytic cells such as monocytes and macrophages, thereby suppressing inflammation after vascular injury. We compared the effect of clodronate liposomes on the macrophage depletion and neointimal formation after carotid artery injury in Apolipoprotein E-deficient mice [ApoE(-) mice]. METHODS: ApoE(-) mice were randomly assigned to the Clodronate Liposomes Group (Clodronate Group, n=7) and Vehicle Liposomes Group (Control Group, n=7). Clodronate (0.1ml/10g) was injected via tail vein starting 2 days (d-2) before left common carotid artery injury with 0.014 inch guidewire, and clodronate injection was repeated every 7 days subsequently (d+5, d+12, d+19, d+26). Three ApoE(-) mice from each group were sacrificed at 2 and 4 weeks after the vessel injury. The percentage of circulating monocytes was calculated with FACS analysis, and the macrophages in the plaque were stained with CD68 antibodies. The 10 sections of carotid artery from bifurcation were obtained, and the plaque volume was measured with Imagepro program. RESULTS: Blood monocyte percentage decrease subsequently after clodronate injection (14.2 ± 2.1% at baseline, 4.6 ± 0.9% at day 1, 1.0 ± 0.3% at day 2, p < 0.001). The macrophage percentage in the plaque area was significantly lower in the Clodronate Group at week 2 (12.0 ± 2.5 vs. 78.7 ± 7.6 mm2, p<0.05) and at week 4 (14.3 ± 1.5 vs. 77.6 ± 4.4 mm2, p<0.05). IL-6 and TNF-α concentrations significantly decreased in the Clodronate Group at week 4 (12.7 ± 2.3 vs. 22.6 ± 3.3 pg/mL, p<0.05 for IL-6 and 16.3 ± 4.0 vs. 40.8 ± 9.5 pg/mL, p<0.05 for TNF-α). Plaque volume was similar at baseline between the 2 groups but was significantly greater in the Control Group at week 2 (0.345 ± 0.063 vs. 0.153 ± 0.053 mm2, p<0.05) and at week 4 (0.320 ± 0.027 vs. 0.167 ± 0.070 mm2, p<0.05). CONCLUSION: Intravenous administration of clodronate liposomes depleted monocytes and macrophages, thereby reducing inflammatory markers and neointimal formation in ApoE(-) mice.


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