diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM13203diaendo-13203Research ArticleОбзорыReviewЗначение окисленных липопротеинов низкой плотности и их рецепторов LOX-1 при сахарном диабете 2 типаThe Significance of Oxidized Low-Density Lipoproteins and Receptors LOX-1 in Type 2 Diabetes Mellitushttps://orcid.org/0000-0002-5477-4920ФетламД. Л.FetlamD. L.

Фетлам Дмитрий Леонидович

Москва

Dmitry L. Fetlam

Moscow

dmfetlam@yandex.ruhttps://orcid.org/0000-0001-6279-2849ЧумаченкоА. Г.ChumachenkoA. G.

Чумаченко Анастасия Геннадьевна - к.б.н.; ResearcherID: B-1531-2015; Scopus Author ID: 357211375453.

Москва

Anastasya G. Chumachenko - PhD in Biology; ResearcherID: B-1531-2015; Scopus Author ID: 357211375453

Moscow

a_chumachenko@mail.ruhttps://orcid.org/0000-0002-5729-9846ПисаревВ. М.PisarevV. M.

Писарев Владимир Митрофанович - д.м.н., профессор; ResearcherID: E-1373-2012; Scopus Author ID: 7006540472.

107031, Москва, ул. Петровка, 25, стр. 2

Vladimir M. Pisarev - MD, PhD, Professor; ResearcherID: E-1373-2012; Scopus Author ID: 7006540472.

Petrovka street, 25/2, 107031 Moscow

vpisarev@gmail.comНИИ общей реаниматологии им. В.А. Неговского, Федеральный научно-клинический центр реаниматологии и реабилитологииРоссияV.A. Negovskiy Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and RehabilitologyRussian Federation202418012025276589597Copyright © Фетлам Д.Л., Чумаченко А.Г., Писарев В.М., 20252025Фетлам Д.Л., Чумаченко А.Г., Писарев В.М.Fetlam D.L., Chumachenko A.G., Pisarev V.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/13203АКТУАЛЬНОСТЬ

АКТУАЛЬНОСТЬ. Сахарный диабет 2 типа (СД2) встречается у 8,5% взрослого населения с тенденцией к увеличению, способствует утяжелению коморбидного фона пациента, приводит к инвалидизации. Возможной персонификации лечения СД2 могут способствовать высокоинформативные прогностические биомаркеры, поиск которых продолжает оставаться актуальным. Характерной особенностью СД2 является дислипидемия. Одним из ее проявлений является накопление в циркуляции повышенной концентрации окисленных липопротеинов низкой плотности (ox-LDL). Специфическими клеточными рецепторами молекул ox-LDL являются рецепторы LOX-1.

ЦЕЛЬ ОБЗОРА

ЦЕЛЬ ОБЗОРА. Суммировать результаты исследований, представленных в публикациях 2010–2024 гг. (PubMed, RSCI) и свидетельствующих о патогенетической роли ox-LDL и их рецепторов LOX-1 в развитии и течении СД2.

МАТЕРИАЛЫ И МЕТОДЫ

МАТЕРИАЛЫ И МЕТОДЫ. Провели поиск более 2800 источников литературы (PubMed), в которых вместе с термином «сахарный диабет», встречаются ключевые слова: ox-LDL (1150 источников) или LOX-1 (159 источников), а также OLR1 (106 источников). Выделили более 60 источников, имеющих непосредственное отношение к СД2 и исследуемым функционально связанным маркерам — рецептору LOX-1 и его лиганду ox-LDL.

РЕЗУЛЬТАТЫ

РЕЗУЛЬТАТЫ. LOX-1 представляет собой рецептор-мусорщик, который использует ox-LDL в качестве основного лиганда. LOX-1 кодируется геном OLR1, расположенным на хромосоме 12 человека. Продукты гена OLR1 характеризуются наличием изоформ, генерируемых в результате сплайсинга или однонуклеотидного полиморфизма. Взаимосвязь ox-LDL и СД2 имеет двунаправленный характер. Возникающая инсулинорезистентность прямо коррелирует со степенью окисления липопротеинов низкой плотности, которая наблюдается более чем у 80% больных и зависит от длительности СД2. Высокое содержание лиганда LOX-1 ox-LDL в плазме ассоциируется с увеличением риска СД2. Предполагается, что механизм такой ассоциации связан с функционально значимой экспрессией LOX-1 на клетках поджелудочной железы. Показано, что β-клетки поджелудочной железы в присутствии ox-LDL увеличивали продукцию индуцируемого раннего репрессора сигнального пути цАМФ — ICER. В результате действия ICER выработка и секреция инсулина прекращались. Увеличение концентрации ox-LDL является патогенетически значимым фактором развития атеросклеротических поражений сосудов, поскольку стимулирует генерацию пенистых клеток. ox-LDL-LOX-1-опосредованные взаимодействия на поверхности сосудов приводят к дисфункции эндотелия с последующим развитием гипоперфузии тканей и органных нарушений.

ЗАКЛЮЧЕНИЕ

ЗАКЛЮЧЕНИЕ. Циркулирующий ox-LDL во взаимодействии с его рецептором LOX-1 вносит значительный вклад в развитие СД2, способствуя его прогрессированию. Увеличенная концентрация ox-LDL в циркуляторном русле повышает риск тяжелого течения СД2, приводя к дисфункции эндотелия и способствуя развитию атеросклеротического поражения сосудов.

INTRODUCTION

INTRODUCTION. Type 2 diabetes mellitus (T2DM) occurs in 8.5% of the adult population with a tendency to increase. A characteristic feature of T2DM is dyslipidemia. One of its manifestations includes accumulation of increased concentration of oxidized low-density lipoproteins (ox-LDL) in circulation. Ox-LDL molecules act on cells through LOX-1 receptors.

THE PURPOSE OF THE REVIEW is to demonstrate results of studies presented in publications of 2010–2024 (PubMed, RSCI) indicating the pathogenetic role of ox-LDL and its LOX-1 receptors in T2DM development and course.

MATERIALS AND METHODS

MATERIALS AND METHODS. In the analysis of more than 2800 literature sources (PubMed), in which together with term “­diabetes mellitus” keywords are found: ox-LDL (1150 sources) or LOX-1 (159 sources), as well as OLR1 (106 sources), 50 sources were identified that are directly related to T2DM and the studied functionally related markers — the LOX-1 receptor and its ligand ox-LDL.

RESULTS

RESULTS. LOX-1 is scavenger receptor that uses ox-LDL as its proper ligand. Gene OLR1 encodes ox-LDL receptor, LOX-1. The linking of T2DM and circulating levels of ox-LDL is bidirectional. The emerging insulin resistance directly correlates with oxidation of low-density lipoproteins, which is observed in more than 80% of patients and depends on the duration of T2DM. High plasma ligand levels are associated with increased type 2 diabetes risk. The mechanism of this association is thought to be related to functionally significant expression of LOX-1 on pancreatic cells. It was shown that pancreatic β-cells in the presence of ox-LDL increased production of the inducible early repressor of the cAMP signaling pathway, ICER. As result of ICER action, insulin production and secretion ceased. Increased ox-LDL concentrations are a pathogenetically significant factor in the development of atherosclerotic vascular lesions, as they stimulate the generation of foam cells. Ox-LDL-LOX-1-mediated interactions on the vascular surface led to endothelial dysfunction with subsequent development of tissue hypoperfusion and organ dysfunction.

CONCLUSION

CONCLUSION. Circulating ox-LDL, in interaction with its receptor LOX-1, makes a significant contribution to the development of T2DM, promoting its progression. Increased concentration of ox-LDL in blood increases the risk of severe T2DM, leading to endothelial dysfunction and promoting the development of atherosclerotic vascular lesions.

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The authors declare that there are no conflicts of interest present.