Tu-P8:296 Effect of sex hormones on atherosclerotic indices in primary culture of female cells

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

“…In monocytes/macrophages, the intracellular cholesterol accumulation was inhibited by estrogens. On the contrary, androgens increased cholesterol accumulation and 3 H-thymidine incorporation [9]. A later communication confirmed that both testosterone and dihydrotestosterone increased intracellular cholesterol content in cultured monocytes/macrophages [8].…”

“…The cell model approach was used for evaluation of sex hormones: the estrogens (not otherwise specified) and testosterone were reported to reduce intracellular cholesterol accumulation by cultured normal and atherosclerotic "intimal mesenchymal cells" in parallel with the 3 H-thymidine incorporation interpreted as a decrease in cell proliferation [9]. Note that considerable lipid infiltration of cells is regarded in general pathology as degeneration that can hardly be expected to be accompanied by an increase in cell proliferation.…”

“…By analogy with familial hypercholesterolemia, it might contribute to atherosclerosis: lipids would be deposited into the intercellular/subendothelial space of the vascular wall, in vulnerable sites with the endothelial barrier damaged by hemodynamic forces or otherwise, within pre-existent vulnerable plaques -so as it happens in vivo in conditions of progressive atherosclerosis. This is the philosophical paradox apparently disregarded by the authors of [1][2][3][4][5][6][7][8][9][10][11][12][13]: 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.…”

“…A well-known problem in laboratory investigations is how to put a biological barrier into a test tube [34]. This problem has not been solved in the experiments under discussion [1][2][3][4][5][6][7][8][9][10][11][12][13].…”

“…The large research series has become internationally known in the 1980s and continues until today [1][2][3][4][5][6][7][8][9][10][11][12][13]. In brief, cultures of smooth muscle or monocyte-derived cells have been used for evaluation of the ability of different substances to enhance or diminish cholesterol deposition in the cells, incubated with the serum from patients with atherosclerosis, which has been interpreted as anti-or pro-atherogenic action.…”