Project Title

3-Dimensional spatial proteomics and degradomics to elucidate rupture mechanisms and improve diagnosis of human atherosclerotic plaques

Background

Atherosclerosis is a major cause of cardiovascular disease and is characterized by arterial wall dysfunction, lipid accumulation, ongoing chronic inflammation, cell death etc. resulting in plaque formation. Plaques are highly heterogenous, and this is strongly associated with their propensity to undergo rupture. The nature and extent of this heterogeneity, and its influence on plaque rupture is a major knowledge gap.

Aim

This project aims to elucidate the mechanisms behind plaque rupture and thereby improve diagnostics and outcome in patients with atherosclerosis. Additionally, we hope to discover possible novel biomarkers for early diagnosis.  

Methods

We will be using proteomic and degradomic approaches on carotid atherosclerotic plaques collected from patients to elucidate changes in the protein composition in a spatial manner. The result will, furthermore, be correlated with imaging data and patient outcome data and thereby provide a greater diagnostic picture.  

Preliminary results

Data produced by the Goncalves’ and Davies’ group show that the protein composition of plaques changes in a 3-dimensional manner and that protein composition and enzyme activation affect plaque stability.