Statins represent one of the most widely used classes of drugs in current medicine. In addition to a substantial decrease in atherogenic low density lipoprotein (LDL) particle concentrations, several large trials have documented their potent anti-inflammatory activity. Based on our preliminary data, we showed that statins are able to decrease the proportion of pro-inflammatory macrophages (CD14+16+CD36high) in visceral adipose tissue in humans. In the present study including 118 healthy individuals (living kidney donors), a very close relationship between the pro-inflammatory macrophage proportion and LDL cholesterol levels was found. This was confirmed after adjustment for the most important risk factors. The effect of statins on the proportion of pro-inflammatory macrophages was also confirmed in an experimental model of the Prague hereditary hypercholesterolemia rat. A direct anti-inflammatory effect of fluvastatin on human macrophage polarization in vitro was documented. Based on modifying the LDL cholesterol concentrations, statins are suggested to decrease the cholesterol inflow through the lipid raft of macrophages in adipose tissue and hypercholesterolemia to enhance the pro-inflammatory macrophage phenotype polarization. On the contrary, due to their opposite effect, statins respond with anti-inflammatory activity, affecting the whole organism.

Department of Anesthesia and Intensive Medicine 1st Faculty of Medicine Charles University and University Military Hospital 169 02 Prague Czech Republic

Department of Epidemiology and Biostatistics 3rd Faculty of Medicine Charles University 100 00 Prague Czech Republic

Department of Immunology Faculty of Science Charles University 128 00 Prague Czech Republic

Department of Physiology Faculty of Science Charles University 128 00 Prague Czech Republic

Department of Transplantation Surgery Institute for Clinical and Experimental Medicine 140 21 Prague Czech Republic

Laboratory for Atherosclerosis Research Centre for Experimental Medicine Institute for Clinical and Experimental Medicine 140 21 Prague Czech Republic

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