Effects of Sex Hormones on Intracellular Cholesterol Accumulation and LDL Aggregation

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

“…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]. However, in a recent article by the same research group, the addition of each of the three hormones (estradiol, testosterone, dihydrotestosterone) at a physiological concentration (1 nM) to the culture medium reduced the cholesterol accumulation in monocytes/macrophages [5].…”

“…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.…”

“…According to a personal communication from Dr. Aksenov at the 77th Congress of the European Atherosclerosis Society in Istanbul (2008), the "cell cultures" did not grow. Therefore, it would be correct to define these cells, surviving for several days or weeks in serumcontaining media [8], not as cell cultures but as incubated cells.…”