CORDIS
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CORDIS

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Mechanistic links between rheumatoid arthritis and cardiovascular complications: investigation on inflammation induced alterations in induced pluripotent stem cell-derived cardiomyocytes

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.
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Coordinator

SLASKI PARK TECHNOLOGII MEDYCZNYCH KARDIO-MED SILESIA SPOLKA Z OGRANICZONA ODPOWIEDZIALNOSCIA

Address

Marii Curie Sklodowskiej 10c
41800 Zabrze

Poland

Activity type

Research Organisations

EU Contribution

€ 149 625,60

Project information

Grant agreement ID: 841627

Status

Grant agreement signed

  • Start date

    1 February 2020

  • End date

    31 January 2022

Funded under:

H2020-EU.1.3.2.

  • Overall budget:

    € 149 625,60

  • EU contribution

    € 149 625,60

Coordinated by:

SLASKI PARK TECHNOLOGII MEDYCZNYCH KARDIO-MED SILESIA SPOLKA Z OGRANICZONA ODPOWIEDZIALNOSCIA

Poland