kpcczКомплексные проблемы сердечно-сосудистых заболеванийComplex Issues of Cardiovascular Diseases2306-12782587-9537Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”10.17802/2306-1278-2020-9-2-102-113kpccz-720Research ArticleАНАЛИТИЧЕСКИЙ ОБЗОРANALYTICAL REVIEWКлеточные и тканевые маркеры атеросклерозаCell and tissue markers of atherosclerosishttps://orcid.org/0000-0002-0748-9238КаширскихД. А.KashirskikhD. A.

Каширских Дмитрий Александрович - младший научный сотрудник лаборатории ангиопатологии.

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

dim.kashirsckih@gmail.comhttps://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. - postgraduate student, researcher assistant at the Laboratory of Angiopathology

8, Baltiyskaya St., Moscow, 125315

https://orcid.org/0000-0002-0312-3773СухоруковВ. Н.SukhorukovV. N.

Сухоруков Василий Николаевич - младший научный сотрудник лаборатории инфекционной патологии и молекулярной микроэкологии НИИМЧ, научный сотрудник лаборатории медицинской генетики НМИЦК.

Ул. 3-я Черепковская, 15а, Москва, 121552; Ул. Цюрупы, 3, Москва, 117418

Sukhorukov Vasily N. - researcher assistant at the Laboratory of Infectious Pathology and Molecular Microecology, RIHM; researcher at the Laboratory of Medical Genetics, NMRCC.

15a, 3rd Cherepkovskaya St., Moscow, 121552; 3, Tsyurupy St., Moscow, 117418

https://orcid.org/0000-0003-0978-6444СобенинИ. А.SobeninI. 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, профессор, заведующий лабораторией ангиопатологии НИИОПП, ведущий научный сотрудник лаборатории инфекционной патологии и молекулярной микроэкологии НИИМЧ.

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

Orekhov Alexander N. - PhD, Professor, Head of the Laboratory of Angiopathology, RIGPP; senior researcher at the 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 патофизиологииРоссияResearch Institute of General Pathology and PathophysiologyRussian FederationФедеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр кардиологии» Министерства здравоохранения Российской Федерации; Федеральное государственное бюджетное научное учреждение Научно-исследовательский институт морфологии человекаРоссияFederal State Budgetary Institution “National Medical Research Centerfor Cardiology” of the Ministry of Healthcare of the Russian Federation; Federal State 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 Centerfor 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 Научно-исследовательский институт морфологии человекаРоссияResearch Institute of General Pathology and Pathophysiology; Federal State Scientific Institution Research Institute of Human MorphologyRussian Federation20202406202092102113Copyright © Каширских Д.А., Хотина В.А., Сухоруков В.Н., Собенин И.А., Орехов А.Н., 20202020Каширских Д.А., Хотина В.А., Сухоруков В.Н., Собенин И.А., Орехов А.Н.Kashirskikh D.A., Khotina V.A., Sukhorukov V.N., Sobenin I.A., Orekhov A.N.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.nii-kpssz.com/jour/article/view/720

Атеросклеротические изменения характеризуются различными множественными изменениями на уровне экспрессии генов. Однако существуют общие тенденции на клеточном и молекулярном уровнях. Происходит ремоделирование внеклеточного матрикса сосудов за счет повышения уровней матричных рибонуклеиновых кислот генов катепсинов, металлопротеиназ, а также снижения уровней транскриптов коллагена I и III типа. Изменение транскрипционной активности некоторых генов приводит к нарушению регуляции цитоскелета гладкомышечных клеток и межклеточного взаимодействия, что также вносит свой вклад в образование атеросклеротического поражения. Привлечение лейкоцитов к стенкам артерий при помощи катепсинов, хемокинов и других маркеров, связанных с сигнальными системами, приводит к инфильтрации моноцитов в интиму.

Кроме того, наблюдается изменение соотношения экспрессии апобелков, превалирования экспрессии одних над другими, что приводит к накоплению холестерина и нарушению обмена липидов. Активируются гены, ответственные за накопление окисленных липопротеидов низкой плотности, что индуцирует воспалительные реакции через толл-подобные рецепторы. Наблюдаются высокие уровни CD36 и CD68, сигнализирующие об инфильтрации поражений макрофагами. В обзоре проанализированы результаты недавних исследований, связанных с изучением транскрипто-ма атеросклеротической бляшки из сонной артерии человека. Мы рассмотрели дифференциально экспрессированные гены металлопротеиназ, катепсинов, хемокинов и их рецепторов, липидного метаболизма, компонентов внеклеточного матрикса; рецепторов, связанных с сигнальными системами, маркеров макрофагов и гладкомышечных клеток. Часть исследований имели перекрывающиеся результаты, а также новые гены, ранее не ассоциированные с атеросклерозом. Изучение маркеров атеросклеротической бляшки, отдельных генов сигнальных путей может помочь расширить наши знания о важных путях, вовлеченных в механизм атерогенеза, а также определить потенциальные биомаркеры, характеризующие стадии развития атеросклеротического поражения.

Atherosclerotic lesions are characterized by various multiple changes at the gene expression levels. However, there are general trends at the cellular and molecular levels. Extracellular matrix remodeling of blood vessels occurs due to an increase in the mRNA levels of the cathepsin and matalloprotease genes, as well as a decrease in the levels of type I and III collagen transcripts. A change in the transcriptional activity of some genes leads to a disruption in the regulation of the smooth muscle cells cytoskeleton and intercellular interaction, which also contributes to the formation of atherosclerotic lesions. Attraction of leukocytes to the arterial walls by cathepsins, chemokines and other markers associated with signaling systems leads to the infiltration of monocytes into the intima. In addition, there is a change in the ratio of apoprotein expression, the prevalence of the expression of some over others, which leads to the cholesterol accumulation and impaired lipid metabolism.

The genes responsible for the accumulation of oxidized low-density lipoproteinare activated, that induces inflammatory responses through Toll-like receptors. High levels of CD36 and CD68 are observed, signaling the infiltration of lesions by macrophages. This review focuses on the recent studies on the transcriptome of atherosclerotic plaque from the human carotid artery. We examined differentially expressed genes of metalloproteases, cathepsins, chemokines and their receptors, lipid metabolism, extracellular matrix components, receptors associated with signaling systems, macrophage and smooth muscle cells markers. Several studies have overlapping results, as well as new genes that have not previously been reported to be associated with atherosclerosis. Studying of atherosclerotic plaque markers and single signaling pathway genes can provide new insights into the pathways involved in the mechanism of atherogenesis, as well as identify potential biomarkers that characterize the stages of atherosclerotic lesion development.

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