PMID- 12605015
OWN - NLM
STAT- MEDLINE
DCOM- 20031009
LR  - 20211203
IS  - 0160-2446 (Print)
IS  - 0160-2446 (Linking)
VI  - 41
IP  - 3
DP  - 2003 Mar
TI  - Propagermanium suppresses macrophage-mediated formation of coronary 
      arteriosclerotic lesions in pigs in vivo.
PG  - 372-80
AB  - Although the importance of monocytes/macrophages in the pathogenesis of 
      arteriosclerosis is widely accepted, effective and safe treatment to inhibit 
      those inflammatory cells remains to be developed. It was recently found that 
      propagermanium, which is clinically used for the treatment of chronic hepatitis 
      type B in Japan, markedly suppresses monocyte chemotaxis in response to 
      macrophage chemoattractant protein-1 (MCP-1) through inhibition of its receptor, 
      C-C chemokine receptor 2, in vitro. This prompted examination of whether 
      propagermanium suppresses the macrophage-mediated formation of coronary 
      arteriosclerotic lesions in our porcine model in vivo. It was first confirmed 
      that propagermanium inhibited the migration of porcine monocytes in response to 
      MCP-1 at therapeutic concentrations in vitro. Pigs were randomly divided into two 
      groups; one group was orally treated with propagermanium (1 mg/kg, three 
      times/day) and another group served as a control (n = 6 each). Porcine coronary 
      segment was treated from the adventitia with MCP-1 and oxidized low-density 
      lipoprotein for 2 weeks. In the control group, this treatment resulted in the 
      development of stenotic coronary lesions with hyperconstrictive responses to 
      serotonin where arteriosclerotic lesions (neointimal formation and constrictive 
      remodeling) were developed. Immunohistochemical analysis demonstrated the 
      macrophage accumulation in the adventitia and the media. By contrast, in the 
      propagermanium group, angiographic coronary stenosis, hyperconstrictive 
      responses, histologic changes, and macrophage accumulation were all significantly 
      suppressed. These results indicate that propagermanium suppresses 
      macrophage-mediated formation of coronary arteriosclerotic lesions in vivo, 
      suggesting its potential usefulness for the treatment of arteriosclerotic 
      vascular diseases.
FAU - Shimokawa, Hiroaki
AU  - Shimokawa H
AD  - Department of Cardiovascular Medicine, Kyushu University Graduate School of 
      Medical Sciences, Fukuoka, Japan. shimo@cardiol.med.kyushu-u.ac.jp
FAU - Eto, Yasuhiro
AU  - Eto Y
FAU - Miyata, Kenji
AU  - Miyata K
FAU - Morishige, Kunio
AU  - Morishige K
FAU - Kandabashi, Tadashi
AU  - Kandabashi T
FAU - Matsushima, Kouji
AU  - Matsushima K
FAU - Takeshita, Akira
AU  - Takeshita A
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cardiovasc Pharmacol
JT  - Journal of cardiovascular pharmacology
JID - 7902492
RN  - 0 (Organometallic Compounds)
RN  - 0 (Propionates)
RN  - 00072J7XWS (Germanium)
RN  - 1Q2P9TO9Q7 (propagermanium)
SB  - IM
MH  - Animals
MH  - Coronary Artery Disease/*drug therapy/pathology
MH  - *Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Germanium
MH  - Macrophages/*drug effects/pathology
MH  - Male
MH  - Organometallic Compounds/*pharmacology/therapeutic use
MH  - Propionates
MH  - Swine
EDAT- 2003/02/27 04:00
MHDA- 2003/10/10 05:00
CRDT- 2003/02/27 04:00
PHST- 2003/02/27 04:00 [pubmed]
PHST- 2003/10/10 05:00 [medline]
PHST- 2003/02/27 04:00 [entrez]
AID - 10.1097/00005344-200303000-00005 [doi]
PST - ppublish
SO  - J Cardiovasc Pharmacol. 2003 Mar;41(3):372-80. doi: 
      10.1097/00005344-200303000-00005.