UCARE SIGNED

Project "UCARE" data sheet

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 Project 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.