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CORDIS

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

Project description

The female-specific biology of heart disease

Recent years have witnessed an increase in the hospitalisation and mortality of young women due to coronary artery disease (CAD). The underlying mechanism of CAD pathophysiology in women is atherosclerotic plaque erosion, which leads to missed or delayed diagnosis. The key objective of the EU-funded UCARE project is to prove that diseased vascular tissue and CAD gene expression display sex-related differences. Researchers will study individual cells from plaques to determine the clinically relevant female-specific biology of CAD. The project will provide the necessary evidence to close the diagnostic gap between men and women.

Objective

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. Plaque erosion refers to thrombus formation on top of an intact non-ruptured plaque in the coronary artery.

Early recognition of plaque erosion will, therefore, specifically aid in the diagnosis of CAD in women. However, knowledge on CAD and plaque erosion in women is lagging behind. This is due to the underrepresentation of women in clinical trials for CAD and biobank studies. This gap is now only gradually being recognized in research, but not yet fully addressed as pooling of data from both sexes is still common practice. My research efforts have convincingly contributed to the awareness that sex differences in human diseased vascular tissue are relevant. With my group I have shown that sex differences are specifically evident in regulatory gene networks and key player genes for CAD. This also corresponds with sex-specific epigenetic signatures of atherosclerotic plaques, and human endothelial gene expression patterns.

In UCARE, I propose to utilize vascular tissues and plaque samples from well-powered studies to analyze these by sex to a single-cell level. This approach will identify female-specific key player genes in individual cells of plaques and unravel clinically relevant female-specific biology of CAD and plaque erosion. These findings will be translated to systemically expressed DNA methylation profiles in cell free DNA in plasma to move towards early diagnostics. This is a necessary and challenging step towards closing the diagnostic gap between men and women.

Host institution

UNIVERSITAIR MEDISCH CENTRUM UTRECHT
Net EU contribution
€ 1 999 979,00
Address
HEIDELBERGLAAN 100
3584 CX Utrecht
Netherlands

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Region
West-Nederland Utrecht Utrecht
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 999 979,00

Beneficiaries (1)