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Expression of LOX-1 and NOX1 genes in the human umbilical vein endotheliocytes (HUVECs) cultured in the presence of low-density lipoproteins (LDL) modified with various natural dicarbonyls was investigated for the first time. It was found that among the investigated dicarbonyl-modified LDLs (malondialdehyde (MDA)-modified LDLs, glyoxal-modified LDLs, and methylglyoxal-modified LDLs), the MDA-modified LDLs caused the greatest induction of the LOX-1 and NOX1 genes, as well as of the genes of antioxidant enzymes and genes of proapoptotic factors in HUVECs. Key role of the dicarbonyl-modified LDLs in the molecular mechanisms of vascular wall damage and endothelial dysfunction is discussed. [ABSTRACT FROM AUTHOR]

Nanoparticles of the lipid-transporting system of the organism, low-density lipoproteins (LDL) of blood plasma, are prone to free radical peroxidation with formation of their main modified forms – oxidized LDL itself (containing hydroperoxy-acyls in phospholipids of the outer layer of particles) and dicarbonyl-modified LDL (apoprotein B-100 in which chemically modified via the Maillard reaction). Based on the study of free radical oxidation kinetics of LDLs, it was found that the existing in the literature designation of "oxidized lipoproteins" is incorrect because it does not reveal the nature of oxidative modification of LDLs. It was shown in this study that the "atherogenic" LDLs (particles of which are actively captured by the cultured macrophages) are not the oxidized LDL (in which LOOH-derivatives of phospholipids are formed by enzymatic oxidation by C-15 lipoxygenase of rabbit reticulocytes), but dicarbonyl-modified LDLs. Important role of the dicarbonyl-modified LDLs in the molecular mechanisms of atherogenesis and endothelial dysfunction is discussed. [ABSTRACT FROM AUTHOR]

It has been established that acylhydroperoxy derivatives of phospholipids from oxidized rat liver mitochondria are captured predominantly by LDL particles but not by HDL during co-incubation with blood plasma lipoproteins, which refutes the previously suggested hypothesis about the involvement of HDL in the reverse transport of oxidized phospholipids and confirms the possibility of different mechanisms of lipohydroperoxide accumulation in LDL during oxidative stress. [ABSTRACT FROM AUTHOR]

The kinetics of free radical peroxidation of different classes of blood plasma lipoproteins (nanoparticles involved in lipid transport in the body) was studied. The susceptibility of atherogenic low-density lipoproteins (LDLs) to the Cu2+-initiated free radical peroxidation in vitro was found to be more than ten times higher than that of antiatherogenic high density lipoproteins (HDLs). The baseline content of acyl hydroperoxy derivatives of phospholipids (primary products of free radical peroxidation) in the outer layer of LDL particles in vivo measured per particle exceeded the baseline content of these compounds in HDL particles by more than an order of magnitude. The susceptibility to oxidation of the HDL2 subfraction of HDLs was higher than the susceptibility of total HDL fraction and HDL3 subfraction. The data obtained confirm an important role of free radical peroxidation of LDLs in the molecular mechanisms of vascular wall damage in atherosclerosis. [ABSTRACT FROM AUTHOR]