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Understanding and modulating vascular arrest with ultra-high definition

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.

Field of science

  • /medical and health sciences/clinical medicine/cardiology/cardiovascular diseases

Call for proposal

ERC-2020-COG
See other projects for this call

Funding Scheme

ERC-COG - Consolidator Grant

Host institution

CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III (F.S.P.)
Address
Calle Melchor Fernandez Almagro 3
28029 Madrid
Spain
Activity type
Research Organisations
EU contribution
€ 1 998 500

Beneficiaries (1)

CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III (F.S.P.)
Spain
EU contribution
€ 1 998 500
Address
Calle Melchor Fernandez Almagro 3
28029 Madrid
Activity type
Research Organisations