mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-TRO-3320mimmun-3320Research ArticleОБЗОРЫREVIEWSРОЛЬ ОЛИГОНУКЛЕОТИДНЫХ ПОЛИМОРФИЗМОВ VEGF В РАЗВИТИИ СЕРДЕЧНО-СОСУДИСТЫХ ЗАБОЛЕВАНИЙThe role of single nucleotide polymorphisms of VEGF gene in the development of cardiovascular diseaseshttps://orcid.org/0000-0002-5610-4760ГаффароваА. С.GaffarovaA. S.

ассистент кафедры внутренней медицины №2 Ордена Трудового Красного Знамени Медицинского института имени С.И. Георгиевского Федеральное государственное автономное образовательное учреждение высшего образования «Крымский федеральный университет имени В.И. Вернадского»

Assistant of the Department of Internal Medicine No.2 

Establishment: The Order of the Red Banner of Labor of the S.I. Georgievsky Medical Institute Federal State Autonomous Educational Institution of Higher Education "V.I. Vernadsky Crimean Federal University"

anife.gaffarova96@yandex.ruhttps://orcid.org/0000-0002-5486-7262ЯцковИ. А.YatskovI. A.

к. мед. н, доцент кафедры внутренней медицины №2 Ордена Трудового Красного Знамени Медицинского института имени С.И. Георгиевского Федеральное государственное автономное образовательное учреждение высшего образования «Крымский федеральный университет имени В.И. Вернадского»

PhD, Аssociate professor of the Department of Internal Medicine No. 2 of the Order of the Red Banner of Labor of the S.I. Georgievsky Medical Institute Federal State Autonomous Educational Institution of Higher Education "V. I. Vernadsky Crimean Federal University"

egermd@yandex.ruhttps://orcid.org/0000-0001-9640-754XБелоглазовВ. А.BeloglazovV. A.

д. мед. н., заведующий кафедрой внутренней медицины №2 Ордена Трудового Красного Знамени Медицинского института имени С.И. Георгиевского Федеральное государственное автономное образовательное учреждение высшего образования «Крымский федеральный университет имени В.И. Вернадского»

Doctor of Medicine Sciences, Head of the Department of Internal Medicine No. 2 of the Order of the Red Banner of Labor of the S.I. Georgievsky Medical Institute Federal State Autonomous Educational Institution of Higher Education "V.I. Vernadsky Crimean Federal University"

biloglazov@mail.ruhttps://orcid.org/0000-0003-4590-3580АгееваЕ. С.AgeyevaE. S.

д. мед. н., заведующий кафедрой биологии медицинской Ордена Трудового Красного Знамени Медицинского института имени С.И. Георгиевского Федеральное государственное автономное образовательное учреждение высшего образования «Крымский федеральный университет имени В.И. Вернадского»

Doctor of Medical Sciences, Head of the Department of Biology of the Order of the Red Banner of Labor of the S.I. Georgievsky Medical Institute Federal State Autonomous Educational Institution of Higher Education "V.I. Vernadsky Crimean Federal University"

ageevaeliz@rambler.ruhttps://orcid.org/0000-0002-0766-3144ДоляЕ. М.DolyaE. M.

к. мед. н, доцент кафедры внутренней медицины №2 Ордена Трудового Красного Знамени Медицинского института имени С.И. Георгиевского Федеральное государственное автономное образовательное учреждение высшего образования «Крымский федеральный университет имени В.И. Вернадского»

PhD, Аssociate professor of the Department of Internal Medicine No. 2 of the Order of the Red Banner of Labor of the S.I. Georgievsky Medical Institute Federal State Autonomous Educational Institution of Higher Education "V. I. Vernadsky Crimean Federal University"

dolyalena@yandex.ruОрдена Трудового Красного Знамени Медицинский институт им. С.И. Георгиевского Федеральное государственное автономное образовательное учреждение высшего образования «Крымский федеральный университет имени В.И. Вернадского»РоссияS.I. Georgievsky Medical Institute, Vernadsky Crimean Federal University, Simferopol, Republic of Crimea, RussiaRussian Federation20191111202500Online First3320Copyright © Гаффарова А.С., Яцков И.А., Белоглазов В.А., Агеева Е.С., Доля Е.М., 20192019Гаффарова А.С., Яцков И.А., Белоглазов В.А., Агеева Е.С., Доля Е.М.Gaffarova A.S., Yatskov I.A., Beloglazov V.A., Ageyeva E.S., Dolya E.M.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/3320

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 тромбоцитов.

Семейство факторов роста эндотелия сосудов (VEGF) является важным компонентом ангиогенеза, участвующий 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.

Cardiovascular diseases (CVD) are the main cause of mortality in general population. Pathophysiology underlying CVD development includes inflammation, endothelial dysfunction, oxidative stress, atherosclerosis, fibrosis, dyslipidemia and thromboembolism. Endothelial dysfunction affects the balance of endothelium-dependent vasoconstriction and vasodilation by increasing cytokine levels, adhesion molecule expression, leukocyte and monocyte migration, and platelet activation. The vascular endothelial growth factor (VEGF) family is an important component of angiogenesis involved in inducing migration and proliferation of endothelial cells by modulating vascular permeability and blood clotting. The VEGF family includes 5 proteins, of which VEGF-A, VEGF-B and PlGF (placental growth factor) regulate angiogenesis, and VEGF-C and VEGF-D (c-Fos-induced growth factor, FIGF) regulate lymphangiogenesis. VEGF-A is a key factor in the angiogenesis and collateral circulation (arteriogenesis) mediated by the binding of VEGF-A to the VEGFR-1 (Flt-1) and VEGFR-2 (KDR) receptors. As a result of our search, an increased risk of coronary heart disease is expected in the case of detection of certain single oligonucleotide polymorphisms (SNPs) in VEGF-A gene, in particular: rs3025039, rs699947, rs2010963, rs1570360 and rs7667298.

VEGF-D is a secreted factor that regulates lymphangiogenesis, angiogenesis, and endothelial proliferation through interaction with VEGFR2 (KDR). Some studies have demonstrated an increase in VEGF-D levels caused by rs192812042 and rs234500 polymorphisms in patients with acute and chronic coronary syndromes, thus suggesting the role of VEGF-D in the formation of CVD by involving lymphangiogenesis, as well as modulating angiogenesis. Genotyping of patients at CVD risk with identification of multiple VEGF SNPs will enable timely diagnostics of patients with initially increased risk of developing cardiovascular pathology and prescribe treatment and measures, prevent development of acute cardiovascular pathology and reduce mortality caused by CVD.

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