Preliminary Research Of Designing Drug Screening Model Based On Simulating Microvascular Biofluids

Cardiovascular disease is the leading cause of death worldwide, and rates ofmorbidity and mortality have increased in recent years. The identification of new drugsto treat cardiovascular disease relies on robust disease models to test candidatecompounds in vitro. Current disease models and drug screening platforms rely on singlecell analysis of tissue culture cells. However, these models are far more simplistic thanthe in vivo microenvironment of blood vessels, confounding the ability of these modelsto accurately predict the action of candidate compounds in clinical trials. Here, wepresent a novel in vitro drug screening platform that utilizes co-cultures and low shearstress (LSS) to simulate the microenvironment of the blood vessel wall. Endothelialcells and smooth muscle cells are co-cultured in a reconstructive parallel plate flowchamber to simulate vessel walls and a continuous media pump produces the effects ofLSS. Unlike previous drug screening models that rely on oxidizing agents to producepathological effects in cells, our model more accurately simulates the microenvironmentof the vessel wall. This model additionally reproduces many disease markers that arecharacteristic of vascular disease. Compared with a control (static) group, cells in ourdynamic vascular disease model exhibit abnormal cellular shapes, higher apoptotic rates,and higher cell migration rates. In addition, LSS in our model results in increases inplatelet-derived growth factor, increases in malondialdehyde concentrations, anddecreases in superoxide dismutase concentrations. We further verified the usefulness ofthis model by demonstrating that the clinically important drugs trapidil and SalviaeMiltiorrhizae reduced the above-mentioned disease indices, thus showing that treatmentwith these drugs mitigated the damage caused by LSS. Finally, we demonstrated thatcells in our model absorb different components of Salviae Miltiorrhizae extracts ascompared to cells in the oxidizing stress model.These results suggest that ouranti-vascular disease modeling and drug screening model is a more efficient andselective drug screening platform than previously reported drug screening models.