Development of Antiatherosclerotic Drugs on the Basis of Cell Models: A Comment

Abstract

The large research series has become internationally known in the 1980s and continues until today. Cultures of cultured or incubated smooth muscle cells or monocytes/macrophages were used for the measurement of capacities of substances to enhance or lower intracellular cholesterol deposition, which was interpreted as anti-or pro-atherogenic action. The LDL from patients with coronary atherosclerosis caused a 2-4 times elevation of cholesterol contents within the cultured cells. Incubation with sera or LDL from healthy subjects did not induce cholesterol accumulation. Various drugs and natural substances were found to possess pro-or anti-atherogenic potencies. Anti-atherogenic effect of different preparations of plant origin was reported: if an agent induced intracellular lipid accumulation it was regarded atherogenic and vice versa. However, if a pharmacological agent lowers the uptake of lipids by cells in a culture, it should be expected to increase the blood cholesterol level in vivo. It can be reasonably assumed that a drug, inhibiting cholesterol uptake by cultured cells, would elevate the blood cholesterol level in vivo. By analogy with familial hypercholesterolemia, it might contribute to atherosclerosis: lipids would be deposited into the intercellular/subendothelial space of the vascular wall, in sites with damaged endothelial barrier and vulnerable plaques. The agents supposedly having an anti-atherogenic potency in a cell culture might reduce cholesterol uptake diffusely by entire cell populations contributing thereby to hypercholesterolemia. On the contrary, atherosclerosis is a focal disease, affecting primarily damaged sites of the vascular lining, which would be favored by hypercholesterolemia.