kpcczКомплексные проблемы сердечно-сосудистых заболеванийComplex Issues of Cardiovascular Diseases2306-12782587-9537Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”10.17802/2306-1278-2020-9-2-91-101kpccz-719Research ArticleАНАЛИТИЧЕСКИЙ ОБЗОРANALYTICAL REVIEWМетаболизм холестерина в макрофагахCholesterol metabolism in macrophageshttps://orcid.org/0000-0003-2096-3237ХотинаВ. А.KhotinaV. A.

Хотина Виктория Александровна - аспирант, младший научный сотрудник лаборатории ангиопатологии.

Ул. Балтийская 8, Москва, 125315

Khotina Victoria A. - PhD student, research assistant at the Laboratory of Angiopathology.

8, Baltiyskaya St., Moscow, 125315

nafany905@gmail.comhttps://orcid.org/0000-0002-0312-3773СухоруковВ. Н.SukhorukovV. N.

Сухоруков Василий Николаевич - младший научный сотрудник лаборатории инфекционной патологии и молекулярной микроэкологии.

Ул. Цюрупы 3, Москва, 11741

Sukhorukov Vasily N. - research assistant at the Laboratory of Infectious Pathology and Molecular Microecology.

3, Tsyurupy St., Moscow, 117418

https://orcid.org/0000-0002-0748-9238КаширскихД. А.KashirskikhD. A.

Каширских Дмитрий Александрович - младший научный сотрудник лаборатории ангиопатологии.

Ул. Балтийская 8, Москва, 125315

Kashirskikh Dmitry A. - research assistant at the Laboratory of Angiopathology.

8, Baltiyskaya St., Moscow, 125315

https://orcid.org/0000-0003-0978-6444СобенинИ. А.SobeninL. A.

Собенин Игорь Александрович - доктор медицинских наук, руководитель лаборатории медицинской генетики.

Ул. 3-я Черепковская 15А, Москва, 121552

Sobenin Igor A. - PhD, Head of the Laboratory of Medical Genetics.

15A, 3rd Cherepkovskaya St., Moscow, 121552

https://orcid.org/0000-0002-6495-1628ОреховА. Н.OrekhovA. N.

Орехов Александр Николаевич - доктор биологических наук, заведующий лабораторией ангиопатологии НИИОПП; ведущий научный сотрудник лаборатории инфекционной патологии и молекулярной микроэкологии ННИИМЧ.

Ул. Балтийская 8, Москва, 125315; Ул. Цюрупы 3, Москва, 117418

Orekhov Alexander N. - PhD, Professor, Head of the Laboratory of Angiopathology, RIGPP; Senior Researcher, Laboratory of Infectious Pathology and Molecular Microecology, RIHM.

8, Baltiyskaya St., Moscow, 125315; 3, Tsyurupy St., Moscow, 117418

Федеральное государственное бюджетное научное учреждение Научно-исследовательский институт общей патологии и патофизиологииРоссияFederal State Budget Scientific Institution Research Institute of General Pathology and PathophysiologyRussian FederationФедеральное государственное бюджетное научное учреждение Научноисследовательский институт морфологии человекаРоссияFederal State Budget Scientific Institution Research Institute of Human MorphologyRussian FederationФедеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр кардиологии» Министерства здравоохранения Российской ФедерацииРоссияFederal State Budgetary Institution “National Medical Research Center for Cardiology” of the Ministry of Healthcare of the Russian FederationRussian FederationФедеральное государственное бюджетное научное учреждение Научно-исследовательский институт общей патологии и патофизиологии; Федеральное государственное бюджетное научное учреждение Научноисследовательский институт морфологии человекаРоссияFederal State Budget Scientific Institution Research Institute of General Pathology and Pathophysiology; Federal State Budget Scientific Institution Research Institute of Human MorphologyRussian Federation2020240620209291101Copyright © Хотина В.А., Сухоруков В.Н., Каширских Д.А., Собенин И.А., Орехов А.Н., 20202020Хотина В.А., Сухоруков В.Н., Каширских Д.А., Собенин И.А., Орехов А.Н.Khotina V.A., Sukhorukov V.N., Kashirskikh D.A., Sobenin L.A., Orekhov A.N.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.nii-kpssz.com/jour/article/view/719

Нарушение метаболизма липидов может приводить к развитию патологических процессов. Атеросклероз является хроническим заболеванием, которое характеризуется атеросклеротическими поражениями в результате накопления липидов в стенках магистральных сосудов. Из-за накопления холестерина внутри атеросклеротических поражений макрофаги дифференцируются в пенистые клетки. Поглощение липидов макрофагами может осуществляться рецептор-зависимым путем, в котором принимают участие рецепторы к липопротеинам низкой плотности и скэвенджер-рецепторы SR-A, CD36 и LOX- 1, а также рецептор-независимым - за счет пино- и фагоцитоза. Внутриклеточную регуляцию липидов осуществляют различные ферменты, такие как АСАТ-1 и NCEH, ферменты путей биосинтеза и окисления жирных кислот, а также транскрипционные факторы - SREBP, Nrfl и Nrf2. В регуляции оттока холестерина из клеток решающую роль играют липопротеины высокой плотности и такие белки-переносчики, как ABCA1, ABCG1 и SR-BI. Регуляцию всех участников метаболизма липидов осуществляют различные сигнальные киназные пути, активирующие множество транскрипционных факторов - LXR, RXR, PPARy, NF-kB и другие. Нарушение регуляции процессов внутриклеточного метаболизма, дисбаланс поглощения и оттока холестерина из макрофагов в конечном счете приводят к их дифференцировке в пенистые клетки. Цель данного обзора состоит в описании известных механизмов метаболизма липидов в макрофагах, приводящих к превращению этих клеток в пенистые.

Disturbance of lipid metabolism can lead to the development of pathological processes. Atherosclerosis is a chronic disease characterized by the development of atherosclerotic lesions as a result of the lipid accumulation in the great arterial walls. As a result of cholesterol accumulation by macrophage within the atherosclerotic lesions, they differentiate into foam cells. Macrophage lipid uptake may occur either though the receptor-dependent pathway by low-density lipoprotein receptors and the SR-A, CD36 and LOX-1 scavenger receptors, or the receptor-independent pathway by pinocytosis and phagocytosis. Various enzymes such as ACAT-1 and Abstract    NCEH, enzymes of the biosynthesis and fatty acid oxidation pathways, as well as various transcription factors - SREBP, Nrf1 and Nrf2 participate in the intracellular regulation of lipids. High-density lipoproteins and transporters such as ABCA1, ABCG1 and SR-BI play a vital role in the regulation of cholesterol efflux from cells. Players of lipid metabolism are regulated by various kinase signaling pathways that activate many transcription factors - LXR, RXR, PPARy, NF-kB, etc. Regulation disturbance of intracellular metabolism and imbalance in uptake and efflux of cholesterol from macrophages lead to their differentiation into foam cells. The aim of this review is to describe the mechanisms underlaying lipid metabolism in macrophages and resulting in the transformation of these cells into foam cells.

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