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Understanding and modulating vascular arrest with ultra-high definition

Project description

Unlocking endothelial cell biology

Existing therapies against cardiovascular disease often aim to stimulate functional angiogenesis through the delivery of vascular growth factors. This is considered to be beneficial for angiogenesis as it increases endothelial cell proliferation and sprouting. However, highly mitogenic environments also cause a significant cell-cycle arrest of endothelial cells. The EU-funded AngioUnrestUHD project will use advanced genetic methods and single-cell profiling to modulate and elucidate the mechanisms responsible for this arrest. The therapeutic targeting of these mechanisms may enable a more effective induction of angiogenesis in cardiovascular disease or its inhibition in cancer or other vascular disorders.

Objective

Therapeutic modulation of vascular cell proliferation and migration is essential for the effective inhibition of angiogenesis in cancer or its induction in cardiovascular disease. The current view is that an increase in growth factor levels or mitogenic stimulation is beneficial for angiogenesis, since it leads to an increase in both endothelial proliferation and sprouting.

Through the use of innovative genetic and imaging approaches, we have recently elucidated a previously unappreciated, context-dependent mechanism whereby highly mitogenic environments can be detrimental for angiogenesis and lead to the cell-cycle arrest of endothelial cells (ECs), which ultimately impairs vascular growth.

The identified mechanism may explain the failed or inefficient promotion of functional angiogenesis by vascular growth factor delivery therapies, such as those used to treat ischemic cardiovascular disease. We propose that a better understanding and modulation of the identified hypermitogenic arrest process may allow angiogenesis to be induced more effectively.

Taking advantage of recent advances in DNA synthesis, CRISPR gene editing, microscopy and single-cell profiling technologies, we have developed new genetic tools, animal models and methods of broad relevance that enable the study of gene function with higher reliability, throughput and definition.

We propose to use these novel research tools and methods to significantly increase understanding of the biology of blood vessels in distinct physiological and pathological contexts.

We will then use this new knowledge to identify better strategies to promote vascular development in ischemic cardiovascular disease, heal vascular malformations, or inhibit angiogenesis in tumours.

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-COG - Consolidator Grant

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Call for proposal

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(opens in new window) ERC-2020-COG

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Host institution

CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III (F.S.P.)
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 998 500,00
Address
CALLE MELCHOR FERNANDEZ ALMAGRO 3
28029 Madrid
Spain

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Region
Comunidad de Madrid Comunidad de Madrid Madrid
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 998 500,00

Beneficiaries (1)

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