Korean Circ J.  2008 May;38(5):244-249. 10.4070/kcj.2008.38.5.244.

Macrophage Depletion by Clodronate Liposomes Suppresses Neointimal Formation After Carotid Artery Injury in Apolipoprotein E-Deficient Mice

• Hong SJ
• Ahn TH
• Shim WJ
• Park SM
• Choi JI
• Park JS
• Lim SY
• Lim DS
• Park CG
• Seo HS

• KMID: 2225785
• DOI: http://doi.org/10.4070/kcj.2008.38.5.244

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)-alpha 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-alpha). 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 mm2, 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.

Keyword

Clodronate; Macrophages; Inflammation

MeSH Terms

Administration, Intravenous
Animals
Apolipoproteins
Apolipoproteins E
Carotid Arteries
Carotid Artery Injuries
Carotid Artery, Common
Clodronic Acid
Inflammation
Interleukin-6
Interleukins
Liposomes
Macrophages
Mice
Monocytes
Phagocytes
Tumor Necrosis Factor-alpha
Vascular System Injuries
Veins
Apolipoproteins
Apolipoproteins E
Clodronic Acid
Interleukin-6
Interleukins
Liposomes
Tumor Necrosis Factor-alpha

Figure

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  Fig. 1 The percentages of peripheral monocytes decreased dramatically 48 hours after the clodronate liposomes injection.

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  Fig. 2 Cross sections of the carotid arteries of the ApoE (-) mice. Representative cross sections of the ApoE (-) mice common carotid arteries taken 4 weeks after guidewire injury demonstrated decreased neointimal formation in the clodronate group (B, D, F and H). Hematoxylin and eosin-staining (A and B), Masson's Trichrome staining (C and D), CD 68 monoclonal Ab staining (E and F) and elastin staining (G and H) are shown with a bar (250 µm).

• 

  Fig. 3 The plaque volume was significantly greater in the control group at week 2 and at week 4.

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