Uncovering the epigenetic signature of female-specifiC biological networks and key driver genes of coronary ArteRy diseasE

Projektinformationen

UCARE

ID Finanzhilfevereinbarung: 866478

DOI

10.3030/866478

Projekt abgeschlossen

EK-Unterschriftsdatum 16 März 2020

Startdatum 1 September 2020

Enddatum 31 August 2025

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten

€ 1 999 979,00

EU-Beitrag

€ 1 999 979,00

Koordiniert durch

UNIVERSITAIR MEDISCH CENTRUM UTRECHT
Netherlands

Periodic Reporting for period 3 - UCARE (Uncovering the epigenetic signature of female-specifiC biological networks and key driver genes of coronary ArteRy diseasE)

Berichtszeitraum: 2023-09-01 bis 2025-02-28

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

Cardiovascular disease in women is understudied due to underrepresentation in clinical studies. This underrepresentation has led to serious questions around diagnosis and treatment of cardiovascular disease in women as pathophysiology of the disease has different characteristics compared to men.
In this project, we aim to unravel these sex differences and translate female-specific biology to blood diagnostics to improve the diagnoses of heart diseases in women.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

Cardiovascular disease causes 51% of deaths in women and 42% of deaths in men in Europe. Women are contributing mostly to the worrying trend of increases in hospitalizations for coronary artery disease (CAD) at younger ages. Missed and delayed diagnoses in women are more common than in men, as the pathophysiology of CAD in women is different than in men. Men often have atherosclerotic plaque rupture as underlying mechanism for CAD whereas women more often suffer from plaque erosion. Knowledge on mechanisms that explain the sex differences in CAD and plaque erosion is lagging behind. This is due to the underrepresentation of women in clinical trials for CAD and biobank studies.
In the last year, my team has made substantial progress in the elucidation of sex-specific mechanisms driving atherosclerotic disease. We identified important sex differences in gene regulation of atherosclerosis in humans pointing to crucial involvement of smooth muscle cells in atherosclerosis development. Our data suggest that cell phenotypic switching is a dominant feature in female atherosclerosis (Hartman et al. Circulation 2021). Next steps are to understand how these sex differences arise, whether these are driven by sex hormones and their receptors, or sex chromosomes. In addition, we will further identify biomarker profiles that relate to plaque erosion in women.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

While this project focusses on atherosclerosis, mulitple other heart disease have sex-specific characteristics as well. Heart failure with preserved ejection fraction, coronary microvascular dysfunction, coronary dissections are all more prevalent in women as compared to men. During this project, we aim to understand if the mechanisms underlying sex differences found in atherosclerosis may also play a role in the other pathologies.

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