Project description
Targeting vascular calcification in kidney disease
High phosphate levels in the blood often cause blood vessels to become stiff and mineralised, leading to a condition known as vascular calcification. Serving as a key contributor to atherosclerosis and cardiovascular disease, treatment of vascular calcification has low success. Recent evidence suggests that the calcium-sensing receptor (CaSR), a protein involved in mineral balance, may help prevent calcification in blood vessels. With the support of the Marie Skłodowska-Curie Actions programme, the AtheroCaSR project aims to investigate how the activation of CaSR affects vascular and bone health in chronic kidney disease (CKD). Using preclinical models and patient samples, researchers plan to uncover new therapeutic strategies that reduce cardiovascular complications in CKD and ultimately lower mortality.
Objective
The principal cause of death in chronic kidney disease (CKD) patients is cardiovascular disease (CVD). Current therapies to treat vascular calcification (VC) and atherosclerosis, which mainly target mineralization and hyperlipidaemia, are not fully effective and have considerable limitations; therefore, additional mechanisms must be investigated. In this respect, hyperphosphatemia is associated with CVD and mortality in CKD patients. Recently, it has been demonstrated that phosphate inhibits Calcium Sensing Receptor (CaSR) signalling, which arise the hypothesis of a direct CaSR implication in vascular (patho)-physiology. Moreover, CaSR promotes opposed effects in vascular smooth muscle cells (VSMC) and osteoblast, preventing calcification in VSMC while increasing mineralization in osteoblast. Given the accumulative evidences that CaSR may exert protective vascular effects, the aim of the AtheroCaSR project is to study whether CaSR activation prevents vascular disorders while preserving bone health. To address this aim, the effects of CaSR modulation will be tested in vitro on VSMC calcification and osteoblastt differentiation under CKD conditions. Then, the effects of the specific CaSR deletion in VSMC will be studied on VC and atherosclerosis in mice with renal insufficiency using novel novel Next-Generation Sequencing for analysis of single cell transcriptome and translational efficiency, with focus on vascular lesions and mineral metabolism. In addition, whether calcimimetics prevent VC and atherosclerosis will be investigated in mice with reduced renal function. Finally, if CaSR modulation directly reduces VSMC microcalcification and atheromatous plaque will be analysed in a cohort of CKD patients treated with calcimimetics. The results from this ambitious study will provide new knowledge on the vascular pathology in CKD and may encourage promising clinical trials and the development of new drugs, having a great impact on CVD-associated mortality in CKD.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- social sciences sociology demography mortality
- medical and health sciences basic medicine physiology pathophysiology
- natural sciences chemical sciences inorganic chemistry alkaline earth metals
- medical and health sciences clinical medicine cardiology cardiovascular diseases arteriosclerosis
- medical and health sciences basic medicine pathology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2024-PF-01
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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.
CF10 3AT CARDIFF
United Kingdom
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.