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Mechanisms of vascular maturation and quiescence during development, homeostasis and aging

Mechanisms of vascular maturation and quiescence during development, homeostasis and aging

Objective

Angiogenesis research has focused on the sprouting of new capillaries. The mechanisms of vessel maturation are much less well understood. Yet, the maintenance of a mature, quiescent, and organotypically-differentiated layer of endothelial cells (ECs) lining the inside of all blood vessels is vital for human health. The goal of ANGIOMATURE is to identify, validate, and implement novel mechanisms of vascular maturation and organotypic EC differentiation that are active during development, maintenance of vascular stability in adults, and undergo changes in aging. We recently identified previously unrecognized gene expression signatures of vascular maturation in a genome-wide screen of ECs isolated from newborn and adult mice. Epigenetic mechanisms were identified that control the EC transcriptome through gain and loss of DNA methylation as well as EC differentiation and signaling specification. These findings pave the way for groundbreaking novel opportunities to study vascular maturation. By characterizing functionally diverse types of blood vessels, including continuous ECs in lung and brain and sinusoidal ECs in liver and bone marrow, the ANGIOMATURE project will (1) determine up to single cell resolution the transcriptional and epigenetic program(s) of vascular maturation and organotypic differentiation during adolescence, (2) analyze the functional consequences of such program(s) in differentiated ECs and their adaptation to challenge, and (3) study changes of maturation and differentiation program(s) and vascular responses during aging. We will towards this end employ an interdisciplinary matrix of approaches involving omics, systems biology, conditional gene targeting, organoid cell culture, and experimental pathology to create a high-resolution structural and functional organotypic angioarchitectural map. The project will thereby yield transformative mechanistic insights into vital biological processes that are most important for human health and healthy aging.
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Host institution

RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG

Address

Seminarstrasse 2
69117 Heidelberg

Germany

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 275 000

Beneficiaries (2)

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RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG

Germany

EU Contribution

€ 1 275 000

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG

Germany

EU Contribution

€ 1 063 918

Project information

Grant agreement ID: 787181

Status

Ongoing project

  • Start date

    1 August 2018

  • End date

    31 July 2023

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 2 338 918

  • EU contribution

    € 2 338 918

Hosted by:

RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG

Germany