H2020Индивидуална стипендия2019–2022

ADAPT2FLOW · Adaptive and maladaptive endothelial cell dynamics during blood flow-driven vascular patterning

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2019-10-01 → 2022-01-28
Финансиране от ЕС: 147 815 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Ендотелните клетки и тяхното движение срещу кръвния поток определят как се формират кръвоносните съдове, например при артериовенозните малформации. Разбирането на тези процеси помага за разработването на нови терапии за възстановяване след съдови заболявания и превенция на инсулти.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Adaptive and maladaptive endothelial cell dynamics during blood flow-driven vascular patterning

The formation of a functional patterned vascular network (well-defined arteries, veins, and capillaries) is essential for blood vessel functioning and global health. Several human vascular disorders arise from the mis-patterning of blood vessels, such as arteriovenous malformations, aneurysms, and diabetic retinopathy. Blood flow is recognized as the main inducer for vascular patterning, yet very little is known about the molecular mechanisms that vascular patterning. Endothelial cells (the cells bordering vessels) polarize and migrate against the blood flow direction. Yet, how this behavior contributes to the overall process of vascular patterning is completely unknown. It is essential to decipher how endothelial cell polarization and migration against blood flow contributes to vascular patterning as it will provide leads to produce new treatments. Indeed, those new therapies will allow improving the recovery of vascular diseases and might help to prevent some to occur like strokes in predisposed patients. This project aimed to study the dynamics of endothelial cells in vascular patterning during development, normal blood vessel functioning, and disease. Thanks to this action, we developed new tools to study endothelial cell dynamics in vascular patterning in developing and developed vascular networks. We identified an important competition between blood flow and VEGF (an essential factor of blood vessel development) in the control of these dynamics in the developing networks. More interestingly, we also developed a new model for a known vascular disorder that is arteriovenous malformations, and demonstrated that some cellular behaviors are essential to their formation and their resolution which could lead the scientific community to the production of pro-resolution treatments for patients with identified arteriovenous malformations.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

The formation of a functional patterned (adaptation) vascular network is essential for development, tissue growth, and organ physiology. Several human vascular disorders arise from the mis-patterning (maladaptation) of blood vessels, such as arteriovenous malformations, aneurysms, and diabetic retinopathy. Blood flow is recognized as the main inducer for vascular patterning, yet very little is known about the molecular mechanisms that vascular patterning.C. Franco and others recently highlighted that endothelial cells polarize and migrate against the blood flow direction. Yet, how this behavior contributes to the overall process of vascular patterning is completely unknown. This project aims to study the dynamics of endothelial cells in vascular patterning during development, homeostasis, and disease. Taking advantage of a unique new transgenic mouse line reporting endothelial cell polarity in vivo, I will investigate endothelial cell behavior in vivo, including endothelial cell polarity, collective and individual migration and cell rearrangements, using 2-photon microscopy. I will extend this analysis to understand the involvement of endothelial flow-dependent polarity in formation and development of arteriovenous malformations. Finally, I will perform an in vivo functional screen to identify novel regulators of endothelial flow-dependent polarity, using a combination of automated image analysis and hemodynamics modelling.This integrative approach, based on high-resolution imaging and unique experimental models, will provide a unifying model defining the cellular and molecular principles involved in adaptive and maladaptive endothelial cell dynamics during blood flow-driven vascular patterning. Given the physiological relevance of vascular patterning in health and disease, this research plan will set the basis for the development of novel clinical therapies targeting vascular disorders.

Оригинален текст от CORDIS (на английски).

Участници

INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES · LisboaКоординаторПортугалия