H2020Индивидуална стипендия2021–2023

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

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период
2021-03-01 → 2023-09-28
Финансиране от ЕС
149 626 €
Участници
2
Схема
MSCA-IF

Линиите свързват координатора с партньорите. За проекти отпреди 2014 г. CORDIS не винаги дава точни координати. Тези точки са на ниво град или държава.

Накратко на български

Връзката между ревматоидния артрит и сърдечните проблеми се изследва чрез моделиране на човешки сърдечни клетки. Това помага да се разберат молекулните механизми, които повишават риска от инфаркт и сърдечни заболявания при пациенти с артрит.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

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

Rheumatoid arthritis (RA) is a chronic and progressive inflammatory disease of the joints characterized by synovial inflammation and destruction of cartilage and bone. There is increasing awareness that RA is not only limited to the local joint inflammatory state. Of emerging significance is the relationship between RA and systemic inflammation which increases damage to cardiac and endothelial cells. This is coupled with impaired heart and vascular functions, thus contributing to the risk of cardiovascular disease (CVD). Subsequently, CVD is the main cause of the excess morbidity and mortality risk as RA patients may have cardiac problems within one year following diagnosis. Moreover, the risk of having a heart attack and other forms of coronary heart disease increases by 60% in one to four years after the RA diagnosis. Although this recognition has been described by clinicians, the exact reason for the increased CV risk in RA patients is still under intense study. In addition, a novel biological medication used to treat RA may modulate CV risk, therefore should be addressed in cardiovascular drug toxicity. For this reason, the main objective of this project was to generate a novel cellular tool that may help to identify more specific molecular mechanisms associated with the development of heart complications in RA patients. To date, most of the RA research has been traditionally based on a variety of in vitro assays and animal models which may not entirely recapitulate extra-articular manifestations and drug responses. In turn, human cardiomyocytes are difficult to access from the heart of RA patients. Therefore, in this project, we implemented the modern technology of induced pluripotent stem cells (iPSC), pioneered by Shinya Yamanaka’s lab in Kyoto, Japan, who was awarded the 2012 Nobel Prize. iPSCs are a type of stem cell that can be generated directly from adult cells like fibroblasts or blood cells. iPSCs have the same properties as embryonic stem cells, i.e., self-renewing and pluripotent differentiation giving rise to many other cell types, such as neurons, heart, pancreatic, and liver cells. Therefore, nowadays iPSCs have become an important tool for modeling and investigating many human diseases, for screening drugs, and in the field of regenerative medicine.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

  • UNIWERSYTET JAGIELLONSKI · KrakowКоординаторПолша
  • SLASKI PARK TECHNOLOGII MEDYCZNYCH KARDIO-MED SILESIA SPOLKA Z OGRANICZONA ODPOWIEDZIALNOSCIA · ZabrzeНиво градПолша

Връзки

Данни: CORDIS, © Европейски съюз