The alcohol cholesterol, its biological role during phylogenesis, mechanisms of sterol production by statins, pharmacogenomic factors and diagnostic valididty of low density lipoprotein cholesterol

Hypolipidemic activity of statins is realized by inhibition of the alcohol cholesterol (CL) local pool production in hepatocyte endoplasmic reticulum. Before secretion of very low density lipoproteins (VLDL) into hydrophilic medium of the blood, CL covers the total hydrophobic mass of triglycerides (TG). The smaller the CL content in the monolayer between the enzyme (lipase) and substrate (TG), the higher the parameters of hydrolysis of palmitic and oleic VLDL. Statins act as follows: а) block hepatocyte production and decrease plasma content of nonesterified CL; b) activate TG hydrolysis in palmitic and oleic VLDL, formation of ligand VLDL and their uptake by insulin-dependent cells via apoE/B-100 endocytosis; c) activate TG hydrolysis in linolic and linolenic low density VLDL, formation of ligand low density lipoproteins (LDL) and their uptake by apoB-100 endocytosis; d) reduce blood content of equimolary esterified by the alcohol CL polyenic fatty acids, CL esters and CL-VLDL. Nonphysiological effect of impaired function of trophology (nutrition) on fatty acid (FA) metabolism in a population cannot be abolished by prescribing medicines. For lowering cardiovascular morbidity it is necessary to modify environmental factors, i.e., reduce dietary content of saturated FA (primarily of palmitic), trans-FA and palmitoleic FA to physiological levels and increase dietary content of unsaturated FA. Saturated FA block cellular uptake of unsaturated FA. Deficiency of unsaturated FA and excess of palmitic FA lead to the development of atherosclerosis.