Project description
What is the link between rheumatoid arthritis and cardiovascular disease?
Rheumatoid arthritis (RA) is an autoimmune disorder that primarily affects the joints, causing pain, swelling and stiffness. Intriguingly, RA patients have a higher risk of cardiovascular disease, but the underlying mechanism is poorly understood. The EU-funded CVD in RA project is working under the hypothesis that the inflamed microenvironment of the joints affects the bioenergetics and transcriptome of cardiomyocytes. Researchers will generate induced pluripotent stem cells from RA patients and differentiate them into cardiomyocytes to assess cellular metabolism. Results will unveil key cellular and molecular pathways affected in RA patient cardiomyocytes and pave the way towards novel treatments.
Objective
The aim of this project is to uncover the mechanisms by which patients with rheumatoid arthritis (RA) may have an elevated risk of cardiovascular complications. In particular, we will determine the role of the inflamed joint microenvironment in promoting cellular bioenergetics of cardiomyocytes. We aim to test the hypothesis that cardiomyocytes of RA patients reflect the features of pathological changes that might indicate for the cardiac vulnerability characteristic for this disease. This proposal has three specific objectives: (1) To examine whether exposure of control and RA-specific induced pluripotent stem cells-derived cardiomyocytes (RA-iPSC-CMs) into a joint-like environment recapitulate a cardiac disease-like state; (2) to determine the effect of a joint-like environment on cellular bioenergetics of control and RA-iPSC-derived CMs; and (3) to test whether control and RA-iPSC-CMs can act as a tool to identify potential cardioprotective/cardiotoxic treatment strategies used in RA.
This project proposes a truly translational, bench-to-bedside approach building on the strength of the human RA model. We will establish a unique source of functional cardiomyocytes by reprogramming RA synovial fibroblasts and peripheral blood mononuclear cells to iPSC. To investigate the impact of the joint inflammation on cardiomyocytes’ bioenergetics and transcriptomic profile, the state-of-the-art technologies will be applied. The most advanced cell metabolism analyser will be used to quantify real-time measurements of mitochondrial respiration and glycolysis. Global analysis of mRNA and miRNA transcriptome by RNA-seq will allow identifying new cardiomyocyte-specific genes/pathways that might affect cellular metabolism in RA.
Using iPSC-CMs will provide a unique opportunity to examine the pathophysiology of cardiac involvement in RA and to evaluate whether they may serve as a preclinical platform for precision medicine.
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.
- medical and health sciences clinical medicine rheumatology
- medical and health sciences basic medicine physiology pathophysiology
- natural sciences biological sciences cell biology cell metabolism
- medical and health sciences health sciences personalized medicine
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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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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2018
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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.
31-007 KRAKOW
Poland
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.