mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-ATL-2955mimmun-2955Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESАнтитела к липопротеинам низкой плотности, модифицированным малоновым диальдегидом: содержание в крови и роль в атерогенезеAntibodies to low-density lipoproteins modified by malonic dialdehyde: contents in blood and role in atherogenesishttps://orcid.org/0000-0002-8673-9628ИвановаА. А.IvanovaA. A.

Иванова Анна Андреевна - научный сотрудник отдела биохимии

197022, Санкт-Петербург, ул. Академика Павлова, 12

Тел.: 8 (812) 234-93-41

Anna A. Ivanova, Research Associate, Department of Biochemistry

St. Petersburg

anna.ivantcova@gmail.comДмитриеваА. А.DmitrievaA. A.

Дмитриева А.А. – лаборант-исследователь отдела биохимии

Санкт-Петербург

Dmitrieva A.A., Laboratory Assistant, Department of Biochemistry

St. Petersburg

aleksandra-2001@mail.ruДенисенкоА. Д.DenisenkoA. D.

Денисенко Д.А. – д.м.н., профессор, заведующий лабораторией регуляции липидного обмена

Санкт-Петербург

Denisenko A.D., PhD, MD (Medicine), Professor, Head, Laboratory of Regulation of Lipid Metabolism

St. Petersburg

add@iem.spb.ruФГБНУ «Институт экспериментальной медицины»РоссияInstitute of Experimental MedicineRussian Federation202508012025271131142Copyright © Иванова А.А., Дмитриева А.А., Денисенко А.Д., 20252025Иванова А.А., Дмитриева А.А., Денисенко А.Д.Ivanova A.A., Dmitrieva A.A., Denisenko A.D.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2955

В настоящей работе было определено содержание антител к липопротеинам низкой плотности, модифицированным малоновым диальдегидом, концентрация холестерина циркулирующих иммунных комплексов и количество перекисно-модифицированных липопротеинов низкой плотности в крови здоровых лиц и пациентов с различными проявлениями атеросклероза. Кроме того, изучалось влияние антител к липопротеинам низкой плотности, модифицированным малоновым диальдегидом на взаимодействие таких липопротеинов с макрофагами. Всего обследовано 253 человека: здоровые лица (59 человек), пациенты с доклиническим атеросклерозом (25 человек) и пациенты с ишемической болезнью сердца (169 человек). Установлено, что у пациентов с ишемической болезнью сердца по сравнению со здоровыми лицами и пациентами с доклиническим атеросклерозом повышена концентрация холестерина циркулирующих иммунных комплексов в крови, тогда как содержание окисленных липопротеинов низкой плотности не различалось между группами обследованных. При этом у пациентов с атеросклерозом выявлена положительная корреляция между уровнями в крови окисленных липопротеинов низкой плотности и холестерина циркулирующих иммунных комплексов. Содержание в крови антител класса IgG к липопротеинам низкой плотности, модифицированным малоновым диальдегидом, достоверно снижено у больных с ишемической болезнью сердца по сравнению со здоровыми лицами и пациентами с доклиническим атеросклерозом, тогда как концентрация таких антител класса IgM практически не изменялось у пациентов с атеросклерозом, независимо от его тяжести. Было показано, что специфичные антитела к липопротеинам низкой плотности, модифицированным малоновым диальдегидом, значительно снижали цитотоксичность таких ЛПНП, а также их способность вызывать накопление эфиров холестерина в макрофагах, полученных из мононуклеаров периферической крови человека. Таким образом, полученные данные свидетельствуют о том, что антилипопротеиновые антитела могут оказывать защитное действие, предупреждая гибель клеток и снижая накопление эфиров холестерина в макрофагах при их взаимодействии с модифицированными липопротеинами низкой плотности, т. е. предупреждать формирование пенистых клеток.

In this work, we determined the content of antibodies to low-density lipoproteins modified by malondialdehyde, the concentration of circulating immune complexes cholesterol and oxidized low-density lipoproteins in the blood of healthy individuals and patients with various manifestations of atherosclerosis. In addition, the effect of antibodies to low-density lipoproteins modified with malondialdehyde on the interaction of such lipoproteins with macrophages was studied. 253 persons were examined: healthy individuals (59 people), patients with preclinical atherosclerosis (25 people) and patients with coronary artery disease (169 people). It was found that the concentration of circulating immune complexes cholesterol in plasma was increased in patients with coronary artery disease compared with healthy individuals and patients with preclinical atherosclerosis, while oxidized low-density lipoproteins content did not differ between patients groups. At the same time, a positive correlation oxidized low-density lipoproteins plasma concentration with circulating immune complexes cholesterol content was found in patients with atherosclerosis. The plasma level of IgG antibodies to malondialdehyde-modified lipoproteins was significantly reduced in patients with coronary artery disease compared with healthy people and patients with preclinical atherosclerosis. While the level of IgM antibodies to malondialdehyde low-density lipoproteins practically did not change in patients with atherosclerosis independently of disease severity. It was shown that specific antibodies vastly reduced malondialdehyde low density lipoproteins cytotoxicity and ability to induce cholesterol esters accumulation in macrophages derived from human peripheral blood mononuclear cells. Thus, the data obtained indicate that anti-lipoprotein antibodies may have a protective effect by preventing cell death and reducing the accumulation of cholesterol esters in macrophages when they interact with modified low-density lipoproteins, i.e. prevent the foam cells formation.

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