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

Abstract

Excessive proliferation and migration of human arterial smooth muscle cells (haSMC) are prominent features of both primary atherogenesis, as well as restenosis following interventions, such as balloon angioplasty (PTCA) or stent implantation. Thus, in the last two decades many efforts were made to establish a therapeutic strategy with antiproliferative and antimigratory compounds. A great variety of substances belonging to different drug classes were already tested both in vitro and in vivo but there is still no breakthrough in the prevention or treatment of human arterial vessel diseases. Among the choice of less potent compounds, the main reasons for this failure are 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 the morphology of the arterial vessel wall in vitro. The present paper describes the morphology of fibromuscular-like and atheromatous-like proliferates induced in this model in comparison to human plaques, as well as its practicability for the pre-screening of antiarteriosclerotic compounds. As examples, two chemically different compounds are shown. We found that the described transfilter coculture system is a suitable and well-established model allowing fast and reproducible studies with antiproliferative and antimigratory drugs. The transferral of the results to the human situation on the basis of these complex in vitro-studies seems to be improved when compared to most animal models.