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Молекулярная биология, 2023, T. 57, № 6, стр. 1058-1076

Транскрипционный фактор NRF2 в функционировании эндотелия

Н. Д. Кондратенко a, b, Л. А. Зиновкина c, Р. А. Зиновкин a, b, *

a Научно-исследовательский институт физико-химической биологии им. А.Н. Белозерского, Московский государственный университет им. М.В. Ломоносова
119991 Москва, Россия

b Российский научно-исследовательский медицинский университет им. Н.И. Пирогова, Российский геронтологический научно-клинический центр
129226 Москва, Россия

c Факультет биоинженерии и биоинформатики Московского государственного университета им. М.В. Ломоносова
119991 Москва, Россия

* E-mail: roman.zinovkin@gmail.com

Поступила в редакцию 16.04.2023
После доработки 11.05.2023
Принята к публикации 22.05.2023

Аннотация

Транскрипционный фактор NRF2 – главный регулятор антиоксидантной защиты клетки, активируется под воздействием различных стимулов, таких как окислители и электрофилы, что индуцирует транскрипцию целого ряда генов, продукты которых участвуют в метаболизме ксенобиотиков и способствуют уменьшению окислительного стресса. NRF2 является одним из ключевых транскрипционных факторов, обеспечивающих функционирование клеток эндотелия – слоя клеток, выстилающих внутреннюю полость сосудов. Эндотелий выполняет множество гомеостатических функций: контролирует миграцию лейкоцитов во внутренние ткани, регулирует тромбообразование и сосудистый тонус, а также участвует в ангиогенезе. Нарушение функций эндотелия часто сопровождается воспалением и окислительным стрессом, что может приводить к клеточному старению, а также к гибели клеток путем апоптоза, некроза и ферроптоза. Эндотелиальная дисфункция вносит вклад в развитие таких распространенных сердечно-сосудистых заболеваний, как гипертензия и атеросклероз, а также сахарного диабета. Многие патофизиологические процессы в эндотелии, включая старческие изменения, сопряжены со снижением активности NRF2, что приводит к воспалительной активации и снижению активности систем антиоксидантной защиты клетки. Активация сигнального пути NRF2, как правило, способствует разрешению воспаления и устранению окислительного стресса. В данном обзоре рассмотрено значение NRF2 в осуществлении основных функций эндотелия в норме и патологии, а также преимущества и недостатки активации NRF2 как способа профилактики и лечения сердечно-сосудистых заболеваний.

Ключевые слова: транскрипционный фактор NRF2, эндотелий, старение, воспаление, окислительный стресс, возрастные изменения, атеросклероз, сахарный диабет, ангиогенез

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