Proteoheparan sulfate can be adsorbed to a methylated silica surface in a monomolecular layer via its transmembrane hydrophobic protein core domain. Due to electrostatic repulsion, its anionic glycosaminoglycan side chains are stretched out into the blood substitute solution representing one receptor site for specific lipoprotein binding through basic amino acid-rich residues within their apolipoproteins. The binding process was studied by ellipsometric techniques. LDL was found to deposit strongly at the proteoheparan sulfate, particularly in the presence of Ca2+ thus creating the complex formation proteoglycan-low-density lipoprotein-calcium. This ternary complex buildup may be interpreted as arteriosclerotic nanoplaque formation on the molecular level responsible for the arteriosclerotic primary lesion. Although much remains unclear regarding the mechanism of lipoprotein depositions at proteoglycan-coated surfaces, it seems clear that the use of such systems offers possibilities for investigating lipoprotein deposition at a nanoscopic level under close to physiological conditions. Therefore, we tested the system on its reliability in a biosensor application in order to unveil possible acute pleiotropic effects of the lipid lowering drug fluvastatin. Already with a normal blood Ca2+ concentration, the VLDL/IDL/LDL plasma fraction from a high-risk patient with dyslipoproteinemia and type 2 diabetes mellitus showed beginning arteriosclerotic nanoplaque formation that massively increased at higher Ca2+ concentrations. Fluvastatin, whether applied to the patient (one single 80 mg slow release matrix tablet) or acutely in the experiment (2.2 mumol/1), markedly slowed down this process of ternary aggregational nanoplaque complexation at all Ca2+ concentrations used. This action resulted without any change in lipid concentrations of the patient. Furthermore, after ternary complex build-up, fluvastatin was able to reduce nanoplaque adsorption and size. These immediate effects of fluvastatin have to be taken into consideration while interpreting the results of long-term studies. Altogether, the proteoglycan coated hydrophobic silica surface used in these experiments, mimics the endothelial cell membrane in quite a perfect manner with respect to lipoprotein interactions at the blood-endothelium-matrix interface.