title: Long-term treatment with propagermanium suppresses atherosclerosis in WHHL rabbits.
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.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Eto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
authors.forename: Eriko
authors.initials: E
authors.lastname: Tanaka
authors.forename: Kunio
authors.initials: K
authors.lastname: Morishige
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fuchigami
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Ishiwata
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.forename: Akira
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000473:pathology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D001161:Arteriosclerosis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D002460:Cell Line; D005857:Germanium; D006801:Humans; D009942:Organometallic Compounds / Q000008:administration & dosage*; D011422:Propionates; D011817:Rabbits; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics
chemical_list: C515334:CCR2 protein, human; D009942:Organometallic Compounds; D011422:Propionates; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D011973:Receptors, LDL; D005857:Germanium; C066750:propagermanium