Роль олигонуклеотидных полиморфизмов VEGF в развитии сердечно-сосудистых заболеваний

Сердечно-сосудистые заболевания (ССЗ) являются основной причиной смертности населения. Патофизиологическими процессами, лежащими в основе развития ССЗ, выступают воспаление, эндотелиальная дисфункция, окислительный стресс, атеросклероз, фиброз, дислипидемия и тромбоэмболия. Эндотелиальная дисфункция оказывает влияние на баланс эндотелий-зависимой вазоконстрикции и вазодилатации, повышая уровень цитокинов, экспрессию молекул адгезии, миграцию лейкоцитов и моноцитов, а также активируя тромбоциты. Семейство факторов роста эндотелия сосудов (VEGF) является важным компонентом ангиогенеза, участвующим в индуцировании миграции и пролиферации эндотелиальных клеток, модулируя сосудистую проницаемость и тромбогенность. Семейство VEGF включает 5 белков, из которых VEGF-A, VEGF-B и PlGF (плацентарный фактор роста) регулируют ангиогенез, а VEGF-C и VEGF-D (c-Fos-индуцированный фактор роста, FIGF) – лимфангиогенез. VEGF-A является ключевым фактором в образовании новых кровеносных сосудов (ангиогенезе) и коллатеральном кровообращении (артериогенезе), опосредованном связыванием VEGF-A с рецепторами VEGFR-1 (Flt-1) и VEGFR-2 (KDR). В результате исследований были получены данные о повышении риска развития кардиоваскулярной патологии в случае выявления олигонуклеотидных полиморфизмов (ОНП) VEGF-A, в частности rs3025039, rs699947, rs2010963, rs1570360 и rs7667298. VEGF-D является секретируемым фактором, регулирующим лимфангиогенез, ангиогенез и пролиферацию эндотелия посредством взаимодействия с VEGFR2 (KDR). В исследованиях продемонстрировано повышение уровня VEGF-D, обусловленного ОНП rs192812042 и rs234500, у пациентов с острым и хроническим коронарными синдромами, что свидетельствует о роли VEGF-D в формировании КВР путем вовлечения лимфангиогенеза, а также модуляции ангиогенеза. Генотипирование пациентов с наличием КВР с последующей идентификацией ОНП VEGF позволит своевременно выделять группы пациентов с исходно повышенным риском развития кардиоваскулярной патологии и назначить превентивные методы лечения и мероприятия, предотвратить развитие острой кардиоваскулярной патологии в данной категории пациентов и снизить смертность от ССЗ.

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