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.
This project will characterise proteomic changes within human atherosclerotic plaques, both at the bulk level and spatially within the tissue microenvironment. By unraveling the complex landscape of spatial protein dynamics within the plaque, this work may offer transformative insights into cellular processes and disease mechanisms of atherosclerosis.
For further information about this HALRIC pilot project, please contact:
Luke F. Gamon
University of Copenhagen