PMID- 12067906
OWN - NLM
STAT- MEDLINE
DCOM- 20020703
LR  - 20211203
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 22
IP  - 6
DP  - 2002 Jun 1
TI  - Propagermanium reduces atherosclerosis in apolipoprotein E knockout mice via 
      inhibition of macrophage infiltration.
PG  - 969-74
AB  - Monocyte chemoattractant protein-1 (MCP-1), which binds to C-C chemokine receptor 
      2, has been implicated as the primary source of monocyte chemoattractant function 
      in the early stages of atherosclerosis. Recently, propagermanium, a drug used 
      clinically for the treatment of chronic hepatitis in Japan, has been shown to 
      inhibit C-C chemokine receptor 2 function and suppress monocyte/macrophage 
      infiltration in vitro and in vivo. Given the importance of monocyte infiltration 
      in atherogenesis, the inhibition of it by propagermanium might prevent 
      atherosclerosis. Apolipoprotein E knockout (apoE-KO) mice were fed an atherogenic 
      high cholesterol diet with or without 0.005% propagermanium for 8 or 12 weeks. 
      Although the plasma lipid levels were unchanged by the drug treatment, 
      atherosclerotic lesion area in the aortic root was reduced by 50% in the 
      drug-treated apoE-KO mice compared with the nontreated apoE-KO mice after 8 weeks 
      of cholesterol feeding (0.62+/-0.12 versus 1.27+/-0.07 mm2, respectively; 
      P<0.01). Moreover, the accumulation of macrophages in the lesions was markedly 
      reduced in the drug-treated group (macrophage positive area, 0.23+/-0.06 mm2 
      [drug-treated group] versus 0.67+/-0.07 mm2 [control group]; P<0.01). After 12 
      weeks of cholesterol feeding, atherosclerotic lesion formation in the aortic root 
      and in the descending thoracic aorta was significantly reduced in the 
      drug-treated group. Inhibition of macrophage infiltration by propagermanium 
      prevented the formation of atherosclerotic lesions in apoE-KO mice. This drug may 
      serve as a therapeutic tool for the treatment of atherosclerosis.
FAU - Yamashita, Tomoya
AU  - Yamashita T
AD  - Division of Cardiovascular and Respiratory Medicine, Department of Internal 
      Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
FAU - Kawashima, Seinosuke
AU  - Kawashima S
FAU - Ozaki, Masanori
AU  - Ozaki M
FAU - Namiki, Masayuki
AU  - Namiki M
FAU - Inoue, Nobutaka
AU  - Inoue N
FAU - Hirata, Ken-ichi
AU  - Hirata K
FAU - Yokoyama, Mitsuhiro
AU  - Yokoyama M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Apolipoproteins E)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cholesterol, Dietary)
RN  - 0 (Lipids)
RN  - 0 (Organometallic Compounds)
RN  - 0 (Propionates)
RN  - 0 (Thioglycolates)
RN  - 00072J7XWS (Germanium)
RN  - 1Q2P9TO9Q7 (propagermanium)
SB  - IM
MH  - Abdomen
MH  - Animals
MH  - Apolipoproteins E/*deficiency/*genetics/physiology
MH  - Arteriosclerosis/genetics/pathology/*prevention & control
MH  - Cell Adhesion/drug effects/physiology
MH  - Cell Line
MH  - *Cell Migration Inhibition
MH  - Cells, Cultured
MH  - Chemokine CCL2/antagonists & inhibitors/physiology
MH  - Cholesterol, Dietary/administration & dosage
MH  - Endothelium, Vascular/cytology/drug effects/physiology
MH  - Female
MH  - Germanium/*therapeutic use
MH  - Lipids/blood
MH  - Macrophage Activation/drug effects
MH  - Macrophages/*drug effects/*pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Monocytes/drug effects/physiology
MH  - Organometallic Compounds/*therapeutic use
MH  - Propionates
MH  - Thioglycolates/pharmacology
EDAT- 2002/06/18 10:00
MHDA- 2002/07/04 10:01
CRDT- 2002/06/18 10:00
PHST- 2002/06/18 10:00 [pubmed]
PHST- 2002/07/04 10:01 [medline]
PHST- 2002/06/18 10:00 [entrez]
AID - 10.1161/01.atv.0000019051.88366.9c [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2002 Jun 1;22(6):969-74. doi: 
      10.1161/01.atv.0000019051.88366.9c.