Atherosclerosis is the major cause of cardiovascular disease (CVD) and responsible for ~40% of all deaths in developed countries, with increasing prevalence due to sedentary lifestyles, obesity and metabolic syndrome. The disease is characterized by the formation of complex plaque within the arteries which can lead to fatal complications due to plaque rupture and thrombosis.

Inflammation within the atherosclerotic plaque causes remodeling of the extracellular matrix (ECM) proteins which are responsible for maintaining the structural integrity of the plaque. Enzymes which degrade ECM proteins are associated with disease and increased expression correlates with adverse outcomes. Previous studies have relied on bulk tissue samples, where whole plaques are homogenised prior to proteomic analysis. However, plaques are highly heterogeneous, with increased expression of inflammatory mediators in the shoulder region of the plaque. It is therefore crucial that we understand the dynamics in these tissue microenvironments to identify the mechanisms and potential markers of plaque rupture.

In this project, we have established and validated methods for analysing archived plaque material stored for up to 20 years from human patients. We have been able to study plaques both in bulk (homogenised tissue samples) and spatially on thin tissue sections.
By combining laser capture microdissection (using a laser to isolate tiny pieces of plaque) with high-sensitivity mass spectrometry proteomics (to analyse proteins in very small samples), we have been able to probe microenvironments within plaques in increasing detail. This would not have been possible without access to samples from a well-characterised biobank and the strong synergy between infrastructures at UCPH and LU.

A strong focus of this project was the utilisation of archived biological material, enabling new analyses of existing patient samples. We have demonstrated that rich datasets can be obtained even from small, dissected regions of single thin tissue sections. As a result, we anticipate that future research can be conducted with a reduced need for new sample collection, both from human patients and from extensive animal experiments.The results are currently being integrated with complementary analyses and biobank data to help unravel the complex landscape of protein dynamics within human atherosclerotic plaques.

Scientific article

June 2026 | Can markers predict plaque vulnerability? | Atherosclerosis Journal

For further information about this HALRIC pilot project, please contact:

 

Luke F. Gamon
University of Copenhagen
lgamon@sund.ku.dk