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  • Title: [Atherogenic modification of low-density lipoproteins].
    Author: Sukhorukov VN, Karagodin VP, Orekhov AN.
    Journal: Biomed Khim; 2016 May; 62(4):391-402. PubMed ID: 27562992.
    Abstract:
    One of the first manifestations of atherosclerosis is accumulation of extra- and intracellular cholesterol esters in the arterial intima. Formation of foam cells is considered as a trigger in the pathogenesis of atherosclerosis. Low density lipoprotein (LDL) circulating in human blood is the source of lipids accumulated in the arterial walls. This review considered features and role in atherogenesis different modified forms of LDL: oxidized, small dense, electronegative and especially desialylated LDL. Desialylated LDL of human blood plasma is capable to induce lipid accumulation in cultured cells and it is atherogenic. LDL possesses numerous alterations of protein, carbohydrate and lipid moieties and therefore can be termed multiple-modified LDL. Multiple modification of LDL occurs in human blood plasma and represents a cascade of successive changes in the lipoprotein particle: desialylation, loss of lipids, reduction in the particle size, increase of surface electronegative charge, etc. In addition to intracellular lipid accumulation, stimulatory effects of naturally occurring multiple-modified LDL on other processes involved in the development of atherosclerotic lesions, namely cell proliferation and fibrosis, were shown. Odnim iz naibolee rannikh proiavleniĭ ateroskleroza iavliaetsia vne- i vnutrikletochnoe otlozhenie lipidov, preimushchestvenno éfirov kholesterina, v arterial'noĭ intime. V krovi cheloveka byli obnaruzheny modifitsirovannye lipoproteiny nizkoĭ plotnosti (LNP), kotorye, kak predpolagaetsia, i vyzyvaiut nakoplenie lipidov v arterial'noĭ stenke, to est' iavliaiutsia aterogennymi. V predlagaemom obzore rassmotreny funktsional'nye osobennosti i rol' v aterogeneze vazhneĭshikh raznovidnosteĭ modifitsirovannykh LNP: okislennykh LNP, melkikh plotnykh LNP, élektrootritsatel'nykh i, osobenno, desialirovannykh LNP. Aterogennye LNP obladaiut mnogochislennymi izmeneniiami uglevodnogo, belkovogo i lipidnogo komponentov i mogut byt' nazvany mnozhestvenno-modifitsirovannymi LNP. Mnozhestvennye modifikatsii LNP proiskhodiat v plazme chelovecheskoĭ krovi i predstavliaiut soboĭ kaskad posledovatel'nykh izmeneniĭ v lipoproteinovoĭ chastitse: desialirovanie, poteria lipidov, umen'shenie razmera chastits, uvelichenie poverkhnostnogo élektrootritsatel'nogo zariada i t.d. Avtory sklonny schitat' i privodiat dokazatel'stva togo, chto imenno desialirovanie iavliaetsia kliuchevym i pervichnym zvenom étikh izmeneniĭ i dal'neĭshego razvitiia patologii v kletkakh intimy. Pomimo vnutrikletochnogo nakopleniia lipidov, v rabote predstavleny mekhanizmy usileniia potentsiala aterogennosti mnozhestvenno-modifitsirovannykh LNP: vliianie na proliferatsiiu kletok i fibroz, obrazovanie tsirkuliruiushchikh immunnykh kompleksov i agregatov LNP.
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