Progress in the research of atherosclerosis and restenosis using an in vitro method: Transfilter cocultures with human vascular cells

Excessive proliferation and migration of human arterial smooth muscle cells (haSMC) are prominent features of both primary atherogenesis, as well as r estenosis following interventions, such as balloon angioplasty (PTCA) or st ent implantation. Thus, in the last two decades many efforts were made to e stablish a therapeutic strategy with antiproliferative and antimigratory co mpounds. A great variety of substances belonging to different drug classes were already tested both in vitro and in vivo but there is still no breakth rough in the prevention or treatment of human arterial vessel diseases. Amo ng the choice of less potent compounds, the main reasons for this failure a re the use of unappropriate animal models or animal cell cultures allowing no direct transfer of the results to the human situation. For that reason, the more complex transfilter coculture model was developed and established for the cocultivation of human vascular cells and blood cells to imitate th e morphology of the arterial vessel wall in vitro. The present paper descri bes the morphology of fibromuscular-like and atheromatous-like proliferates induced in this model in comparison to human plaques, as well as its pract icability for the pre-screening of antiarteriosclerotic compounds. As examp les, two chemically different compounds are shown. We found that the descri bed transfilter coculture system is a suitable and well-established model a llowing fast and reproducible studies with antiproliferative and antimigrat ory drugs. The transferral of the results to the human situation on the bas is of these complex in vitro-studies seems to be improved when compared to most animal models.