The work packages
WP1 – Clinical assessment of microvascular cardiac and brain rarefaction in VCI patients
The objectives are to
- deliver a physiological non-invasive in vivo cerebral biomarker for brain capillary density.
- determine neuro-microvascular correlates of the severity of cognitive impairment in VCI.
- determine neuro-microvascular correlates of the extent of white matter hyperintensity volume in VCI.
- correlate between blood markers (including microvesicles) and the above-mentioned imaging biomarker of functional capillary rarefaction
WP2 – Clinical assessment of microvascular cardiac and brain rarefaction in HFpEF patients
The objectives are to
- identify novel non-invasive biomarkers of cardiac functional capillary rarefaction.
- determine the pathophysiological relevance of microvascular alterations in HFpEF and its association with myocardial remodelling and the severity of the disease.
- evaluate the changes in microvascular density in response to therapeutic management in aortic stenosis patients.
- identify novel mediators/ mechanisms involved in myocardial remodelling mediated by microvascular alterations.
WP3 – Clinical assessment of microvascular cardiac and brain rarefaction in elderly patients
The objectives are to
- identify pathophysiological relevance of microvascular alterations in a mixed population that present with comorbidities
- validate machine learning tools on a larger patient population
- identify novel mechanisms mediated by microvascular alterations.
WP4 – Validation of microvascular measurements in ZSF1 rat model
The objectives are to
- validate whether microvascular perfusion as measured by MRI can be used to estimate microvascular density in the brain and heart.
- validate whether non-invasive biomarkers are indicative of reduced vascular density in the heart and/or brain.
- compare gene expression of endothelial cells to that of microvesicle during the rarefaction process to identify a mechanistic role of microvesicles.
WP5 – Impact of co-morbidities on brain microvasculature, blood flow and cognition in an experimental model
The objectives are to
- assess 3D cerebral vascular architecture and blood flow patterns in a rat model of comorbidities.
- assess whether cerebral microvascular rarefaction in the ZSF1 rats is accompanied with a decline in cognitive function.
- identify genes involved in senescence and study their role in microvascular rarefaction using a mouse LOF model.
WP6 – Changes in endothelial cell metabolism in presence of comorbidities
The objectives are to
- understand how the presence of comorbidities changed endothelial cell metabolism.
- investigate the effects of these changes in endothelial cell metabolism on the functioning of the microvasculature.
- identify potential therapeutic targets to prevent microvascular rarefaction amongst metabolism gene pathways.
WP7 – Molecular mechanisms of vessel rarefaction
The objectives are to
- investigate the role of active microvascular regression in the development of microvascular rarefaction.
- investigate how PITX2, a component of vascular regression during development, alters cardiac and neural function.
- investigate how PITX2 alters endothelial cell metabolism.
- investigate whether targets downstream of PITX2 can prevent microvascular rarefaction in the presence of comorbidities.
WP8 – Management
The objectives are to
- ensure proper overall management of the project through the implementation of the project’s governance and decision-making structure.
- strengthen and support the abilities of participants to achieve their objectives, complete milestones on time and provide deliverables.
- facilitate and encourage internal communication between partners.
- monitor the project’s progress by comparing planned and actual activities, and notify the appropriate parties of disparities
- ensure that the contractual obligations and financial aspects of the project are carried out efficiently and in a transparent manner, in accordance with the rules of the European Commission
- advise partners on compliance with EU regulations and their contractual and legal requirements.
- provide effective communication between CRUCIAL and the European Commission.
WP9 – Communication, Dissemination & Exploitation
The objectives are to
- communicate, create awareness and promote CRUCIAL, to the public, scientific / clinical community, hospitals, regulators, policy makers, and charities, patients in the media, and academic, industry and other relevant publications and to be present at conferences and other relevant activities as appropriate.
- disseminate the outputs of research activities from researchers, clinicians/hospitals, pharmaceutical industry/SMEs, charities and regulators.
- create the Microvascular Helix, a virtual technology cluster/community hosted on the Crowdhelix Platform that accelerate the dissemination and exploitation plans and support in achieving CRUCIAL’s project and post project impact objectives.
- create an anticipatory business plan and commercialisation strategy by the end of the project, through consulting with health and pharmaceutical industries, as well as additional subject matter experts on boarded through the project’s Microvascular Helix, to achieve the end goal of advancing the delivery of the project’s innovation towards commercial adoption.
WP10 – Ethics requirements
The objective is to ensure compliance with the ‘ethics requirements’ set out in this work package.
This project has received funding from the SESAR Joint Undertaking under the European Union’s Horizon 2020 research and innovation programme under grant agreement No 848109.