References

vavilov

Вавиловский журнал генетики и селекции

Vavilov Journal of Genetics and Breeding

2500-3259

Institute of Cytology and Genetics of Siberian Branch of the RAS

10.18699/VJ19.527

vavilov-2208

Research Article

РЕПРОДУКТИВНЫЕ ТЕХНОЛОГИИ

PHYSIOLOGICAL GENETICS

Неканонические эффекты вазопрессина в ангиогенезе

Noncanonical effects of vasopressin in angiogenesis

https://orcid.org/0000-0003-0545-4311

Хегай

И. И.

Khegay

I. I.

khegay@bionet.nsc.ru

Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияInstitute of Cytology and Genetics, SB RASRussian Federation

2019

23082019

235575581

2019

Хегай И.И.

Khegay I.I.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://vavilov.elpub.ru/jour/article/view/2208

Молекулярное действие вазопрессина зависит от локализации гормональных рецепторов. Основные регуляторные эффекты вазопрессина реализуются в кровеносном сосудистом русле, мозговом веществе почки и головном мозге. В настоящее время накоплена новая информация по тканеспецифичному распределению рецепторов вазопрессина, требующая обобщения. Тромбоциты и эндотелиоциты, экспрессирующие, соответственно, рецепторы типа V1а и V2, относятся к наименее исследованным гормональным мишеням вазопрессина. Вазопрессин инициирует начальную обратимую стадию активации тромбоцитов, необходимую для взаимодействия с белками внеклеточного матрикса. Адгезия тромбоцитов на эндотелий активирует в клетках секрецию ростовых факторов и ферментов метаболизма гликозаминогликанов внеклеточного матрикса. Тромбоцитарная гиалуронидаза HYAL2 гидролизует мегаполимеры гиалуроновой кислоты, иммобилизованные на эндотелиоцитах, на более короткие фрагменты. В отличие от интактной высокомолекулярной гиалуроновой кислоты с молекулярным весом в несколько мегадальтон, обладающей в целом антиангиогенными свойствами, промежуточные фракции гидролиза гиалуроновой кислоты в диапазоне от 2.5 до 200 килодальтон оказывают стимулирующий эффект на ангиогенез. Межклеточные контакты тромбоцитов и эндотелиоцитов стабилизируются за счет взаимодействия адгезивных трансмембранных гликопротеинов РЕСАМ-1. Образующиеся гетеродимеры РЕСАМ-1 приобретают конформацию с высоким сродством к интегринам αvβ3. Активация интегринов формирует контактные связи эндотелия с фибриллярными белками. Активированные эндотелиоциты секретируют фактор фон Виллебранда и Р-селектин. Эти белки аккумулированы в тельцах Вайбеля–Паладе. Вазопрессин стимулирует цАМФ-зависимый ACAP-регулируемый экзоцитоз телец Вайбеля–Паладе. Секретируемые функционально активные мультимеры фактора фон Виллебранда имеют в своем составе множественные домены связывания с другими белками и гликопептидами и дополнительно усиливают взаимодействие клеток с внеклеточным матриксом. Адгезия на фибриллярный коллаген и мембранные гликопротеины в кооперации с эффектами РЕСАМ-1–αvβ3 интегриновых комплексов фиксирует клеточные агрегаты в окружающем интерстиции и ориентирует миграцию пролиферирующих эндотелиоцитов в направлении локальных градиентов ростовых факторов ангиогенеза. Нейрогормональная регуляция секреторной активности тромбоцитов и эндотелиоцитов функционально связывает пролиферацию и миграцию эндотелиоцитов в процессе ангиогенеза и интегрирует их с адаптивными возможностями организма.

The molecular action of vasopressin depends on the localization of hormonal receptors. The basic physiological effects of vasopressin are manifested in the blood vasculature, renal inner medulla and brain. To date, new information concerning the tissue-specific spreading of vasopressin receptors has been accumulated, and it needs to be summarized. Platelets and endotheliocytes expressing V1a and V2 receptor types, respectively, are related to less investigated targets of the hormone. Vasopressin induces the initial reversible stage of platelet activation, required for interaction with intercellular matrix proteins. Platelet adhesion on endothelium activates cellular secretion of growth factors and enzymes for intercellular matrix glucosamine metabolism. Platelet hyaluronidase HYAL2 hydrolyses high-molecular hyaluronic acid to shorter fragments. Unlike intact hyaluronic acid with a molecular weight of several megadaltons, generally showing distinctive antiangiogenic properties, intermediate fractions of hyaluronan hydrolysis in a range from 2.5 to 200 kilodaltons have a stimulating effect on angiogenesis. Intercellular contacts between platelets and endotheliocytes are stabilized due to adhesive transmembrane glycoprotein PECAM-1 interaction. Resulting PECAM-1 heterodimers acquire conformation with high affinity to integrins αvβ3. Integrin activation forms contact links between endothelium and fibrillar proteins. Activated endotheliocytes secrete von Willebrand factor and P-selectin. These proteins are accumulated in Weibel–Palade bodies. Vasopressin stimulates cAMP-dependent ACAP-regulated exocytosis of Weibel–Palade bodies. von Willebrand factor possesses adhesive properties and additionally accelerates interaction of cells with the intercellular matrix. Adhesion on fibrillar collagen and membrane glycoproteins in cooperation with effects of PECAM-1–αvβ3 integrin complexes fixes cell aggregates in the surrounding interstitium and promotes proliferating endotheliocyte migration in according to the direction of local growth factor gradients during angiogenesis. Neurohormonal regulation of platelet and endotheliocyte secretory activity functionally link proliferation and migration of endotheliocytes during angiogenesis and integrate it according to the adaptive capacity of the entire organism.

вазопрессинрецепторы V1а и V2тромбоцитэндотелиоцитгиалуроновая кислотагиалуронидаза HYAL2белок РЕСАМ-1интегрин αvβ3

vasopressinV1aand V2-receptorsplateletendotheliocytehyaluronic acidhyaluronidase HYAL2protein PECAM-1–integrin αvβ3

This work was supported by State Budgeted Project 0324-2019-0041.

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