Propagermanium suppresses macrophage-mediated formation of coronary arteriosclerotic lesions in pigs in vivo

Hiroaki Shimokawa, Yasuhiro Eto, Kenji Miyata, Kunio Morishige, Tadashi Kandabashi, Kouji Matsushima, Akira Takeshita

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)372-380
Number of pages9
JournalJournal of Cardiovascular Pharmacology
Volume41
Issue number3
DOIs
Publication statusPublished - Mar 1 2003

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Swine
Macrophages
Chemotactic Factors
Monocytes
Adventitia
Therapeutics
CC Chemokines
Proteins
proxigermanium
Arteriosclerosis
Chemokine Receptors
Coronary Stenosis
Chronic Hepatitis B
Chemotaxis
Vascular Diseases
LDL Lipoproteins
Serotonin
Japan
Control Groups

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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Propagermanium suppresses macrophage-mediated formation of coronary arteriosclerotic lesions in pigs in vivo. / Shimokawa, Hiroaki; Eto, Yasuhiro; Miyata, Kenji; Morishige, Kunio; Kandabashi, Tadashi; Matsushima, Kouji; Takeshita, Akira.

In: Journal of Cardiovascular Pharmacology, Vol. 41, No. 3, 01.03.2003, p. 372-380.

Research output: Contribution to journalArticle

Shimokawa, Hiroaki ; Eto, Yasuhiro ; Miyata, Kenji ; Morishige, Kunio ; Kandabashi, Tadashi ; Matsushima, Kouji ; Takeshita, Akira. / Propagermanium suppresses macrophage-mediated formation of coronary arteriosclerotic lesions in pigs in vivo. In: Journal of Cardiovascular Pharmacology. 2003 ; Vol. 41, No. 3. pp. 372-380.
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