HEИндивидуална стипендия2024–2025

PREPARE · PREcision medicine to Prevent ARrhythmic Events in athletes

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

Период: 2024-01-01 → 2025-12-31
Финансиране от ЕС: 188 590 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Механизмите на синдрома с дълъг QT интервал при спортисти се анализират чрез лабораторно създадени сърдечни клетки. Това помага за по-добрата оценка на риска от внезапен сърдечен смърт и търсенето на бъдещи терапии.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

PREcision medicine to Prevent ARrhythmic Events in athletes

Sudden cardiac death in young athletes, although rare, has a major emotional and societal impact. In some cases, dangerous heart rhythm problems occur during intense training in people who otherwise appear healthy. One condition that may contribute to this risk is exercise-induced Long QT Syndrome (exiLQTS). Long QT Syndrome (LQTS) is a disorder of the heart’s electrical system in which the QT interval on the electrocardiogram is prolonged, increasing the risk of life-threatening arrhythmias. In most cases, LQTS is genetically mediated and the QT prolongation is persistent. In exercise-induced LQTS, however, the abnormal electrical pattern appears only during intense training and reverses with detraining. The mechanisms behind this phenomenon were largely unknown, creating uncertainty in clinical decision-making and risk assessment. The PREPARE project aimed to uncover why some athletes develop exercise-induced QT prolongation and what are the potential targets for the future therapies. The project focused on the molecular and cellular mechanisms underlying cardiac function. To achieve this, PREPARE used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), a technology that allows to generate cardiomyocytes in the laboratory from individual athletes. This approach makes it possible to study athlete-specific cardiac cells under controlled “exercise-like” conditions in vitro. The project combined multiple levels of analysis, including clinical data, advanced genetic testing, functional measurements of hiPSC-CMs electrophysiology and large-scale transcriptomic (gene expression) analysis. By integrating these data, PREPARE generated new mechanistic insights into how exercise can trigger reversible electrical abnormalities. Although these discoveries are not immediately translated into clinical treatments, they provide a strong scientific foundation for improved risk stratification, future therapeutic development, and personalized approaches in cardiology.

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

Цел на проекта

Regular physical activity is known to be beneficial for health, can prevent cardiovascular disease and reduce overall mortality. However, high intensity exercise can promote the development of arrhythmias and cause sudden cardiac death. Recently the Prof.Peter Schwartz’s group discovered the phenomenon of exercise-induced Long QT Syndrome (exiLQTS). Affected athletes develop significant QT interval prolongation and repolarization abnormalities on the electrocardiogram during training periods and normalisation occurs during detraining. Clinically, these athletes resemble patients with congenital LQTS, who are known to be severely at risk for life-threatening arrhythmias, but no pathogenic genetic variants in main genes responsible for LQTS were found. Data on how exercise could trigger pathogenic QT prolongation and arrhythmias is limited and thus the possibilities to evaluate potential risks and prevent sudden cardiac death in these young athletes are currently absent. This project will use a precision medicine approach to reveal molecular culprits of exiLQTS by:i)demonstrating that the disease could be recapitulated in vitro using athlete-specific induced pluripotent stem cell-derived cardiomyocytes models;ii)creating a statistical model integrating genetic, electrophysiological, and molecular data;iii)discovering major factors responsible for exiLQTS development and identifying molecular targets for risk stratification and therapy.Results of the study will shed the light on mysterious exercise-related QT prolongation and will contribute to better risk assessment and clinical management of arrhythmias in young athletes.

Оригинален текст от CORDIS (на английски).

Участници

ISTITUTO AUXOLOGICO ITALIANO · MILANOКоординаторИталия