Long-term Treatment with Propagermanium Suppresses Atherosclerosis in WHHL Rabbits

Authors:
  • HSHiroaki Shimokawa
    Hiroaki Shimokawa
  • ETEriko Tanaka
    Eriko Tanaka
  • KMKunio Morishige
    Kunio Morishige
  • MFMasahiro Fuchigami
    Masahiro Fuchigami
  • YIYoshiro Ishiwata
    Yoshiro Ishiwata
  • KMKouji Matsushima
    Kouji Matsushima
  • ATAkira Takeshita
    Akira Takeshita
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Abstract
Macrophages play an important role in the pathogenesis of atherosclerosis, for which monocyte chemoattractant protein (MCP)-1 and CCR2 chemokine receptors may be involved. The authors have recently demonstrated that propagermanium exerts inhibitory effect on the CCR2 receptors. In the current study, the authors examined whether the organic germanium suppresses the MCP-1–induced monocyte migration in vitro and the development of atherosclerosis in WHHL rabbits in vivo. In the in vitro experiment, propagermanium concentration-dependently suppressed the MCP-1–induced migration of THP-1 cells. In the in vivo experiment, 20 WHHL rabbits were randomly divided into two groups; one group was treated with oral administration with propagermanium (9 mg/kg/day) for 3 months, and another group served as a control (n = 10 each). After 3 months, the aorta was isolated and stained with oil red O staining, and neointimal formation was quantified. Macrophage accumulation in the aorta was also evaluated by immunostaining. Long-term treatment with propagermanium did not affect the serum lipid profiles. However, the treatment significantly suppressed the oil red O–positive area of the total aorta (p < 0.05). Similarly, propagermanium significantly suppressed the intimal lesions (maximal intimal thickness and intimal area) and macrophage staining–positive area (all p < 0.05). A significant positive correlation was noted between macrophage staining–positive area and intimal lesions (p < 0.0001). These results indicate that long-term treatment with propagermanium suppresses the development of atherosclerosis in WHHL rabbits, suggesting its usefulness for the treatment of atherosclerotic vascular disease in humans.

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