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Orekhov et al. Vessel Plus 2019;3:3 I http://dx.doi.org/10.20517/2574-1209.2018.80 Page 3 of 14

[9]
Figure 1. Cascade of multiple atherogenic modifications of low-density lipoprotein (LDL) particles. Adopted from , with permission
of healthy subjects; and the serum was prepared from the blood of patient with atherosclerosis. Then the
mixture of LDL and serum was incubated at 37 °C during 72 h.

After 1 h of incubation, sialic acid content of LDL decreased, and desialylated LDL particles appeared. LDL
acquired the ability to induce accumulation of intracellular cholesterol; hence the lipoprotein particles
became atherogenic. After 6 h, lipid content and LDL size were decreased. After 36 h, LDL became more
electronegative. The incubation for 48-72 h caused a decrease in the content of antioxidants; in parallel,
susceptibility of LDL to oxidation was increased, leading to the oxidation of the lipoprotein particles.
Prolonged incubation led to degradation of apoproteins. The experiments described above allow us to
conclude that desialylation is the first known modification that leads to the acquisition of atherogenic
properties by LDL particles. Subsequent modifications, such as decrease of the lipid content and particle size,
increase of the particle density and electronegativity further enhanced the LDL atherogenicity. Oxidative
modification of lipoprotein particles occurs at the last stages of a cascade of events of sequential multiple
modifications.

Despite the fact that LDL modification involves changes in different physical and chemical properties in
lipoprotein particle, oxidation is still considered to be the main or even the only atherogenic modification.
Currently, PubMed lists 9,765 publications indexed under “oxidized LDL”, and 4,728 under “oxidized
LDL and atherosclerosis”. More than a thousand review articles on oxidized LDL have been published.
It is generally accepted that oxidized LDL accumulating in the vascular wall triggers atherogenesis [5,9,10] .
[3]
Although oxidized LDL was detected in the vascular wall , for a long time it could not be detected in the
bloodstream. This gave rise to the idea that LDL oxidation does not occur in the blood but takes place in the
vascular wall. There is no need for such an assumption since, as mentioned above, a marker for evaluation