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.