Macrophage depletion by clodronate liposomes suppresses neointimal formation after carotid artery injury in apolipoprotein E-deficient mice

Jun Hong Soon, Hoon Ahn Tae, Joo Shim Wan, Mi Park Seong, Il Choi Jong, Suk Park Jae, Yup Lim Sang, Do Sun Lim, Gyu Park Chang, Seog Seo Hong

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background and Objectives: Clodronate liposomes deplete phagocytic cells, thereby suppressing inflammation after vascular injury. We compared the effect of clodronate liposomes on macrophage depletion and neointimal formation in apolipoprotein E-deficient mice [ApoE (-) mice]. Materials and Methods: ApoE (-) mice were randomly assigned to the clodronate liposomes group (Clodronate Group, n = 7) and the vehicle liposomes group (Control Group, n=7). Clodronate (0.1 mL/10 g) was injected via the tail vein starting 2 days (d-2) before left common carotid artery injury. Results: The percentage of blood monocytes was subsequently decreased after clodronate injection (14.0 ± 7.4% at baseline, 6.8 ± 4.9% at 24 hours and 0.7 ± 0.3% at 1 week after the clodronate liposome injection). The percentage of macrophages in the plaque area was significantly lower in the clodronate group at week 2 (32.0 ± 6.5 vs. 68.7 ± 7.6%, respectively, p < 0.05) and at week 4 (37.3 ± 8.5 vs. 62.6 ± 9.4%, respectively, p < 0.05). The interleukin (IL)-6 and tumor necrosis factor (TNF)-α concentrations were significantly decreased in the clodronate group at week 4 (12.3 ± 2.5 vs. 22.9 ± 3.5 pg/mL, respectively, p < 0.05 for IL-6 and 16.6 ± 2.2 vs. 43.6 ± 6.1 pg/mL, respectively, p < 0.05 for TNF-α). The plaque volume was significantly greater in the control group at week 2 (0.345 ± 0.063 vs. 0.153 ± 0.053 mm2, respectively, p < 0.05) and at week 4 (0.320 ± 0.027 vs. 0.167 ± 0.070 mm 2, respectively, p < 0.05). Conclusion: Intravenous administration of clodronate liposomes depleted monocytes and macrophages, and so this reduced the inflammatory markers and neointimal formation in ApoE (-) mice.

Original languageEnglish
Pages (from-to)244-249
Number of pages6
JournalKorean Circulation Journal
Volume38
Issue number5
DOIs
Publication statusPublished - 2008 May

Keywords

  • Clodronate
  • Inflammation
  • Macrophages

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

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