ENDLESS

Atherosclerotic plaque erosion leading to thrombus formation. The role of extracellular vesicles in endothelial transdifferentiation, apoptosis and leucocyte and platelet adhesion.

Welcome to the website of the ERA-CVD consortium ENDLESS.

 

You will find useful information about the aim of our project, members and newest results.


Introduction

 

The scientific community has faced an impressive shift in incidence and clinical presentation of atherosclerotic disease over the last two decades. Mortality rates due to myocardial infarctions (MI) have decreased by nearly 50% and clinical presentation deviated away from a predominance of STEMI towards NSTEMI.

 

In line with the shift in clinical presentation there has been a significant change in the underlying pathology of symptomatic atherosclerotic lesions that is gradually shifting from the lipid rich unstable plaque towards more stable, fibrous and less inflammatory plaques.

 

This paradigm shift mandates uncovering the mechanisms that accelerate a thrombotic event on top of a stable plaque. The endothelial cell plays a crucial role in leucocyte and platelet adhesion that promote luminal thrombosis, even in the absence of plaque rupture.

 

ENDLESS will unravel mechanisms that lead to endothelial desquamation or transdifferentiation (EndoMT) and explain the thrombotic event that is superimposed on a stable non-ruptured plaque.

 

We will study how coronary artery disease susceptibility genes affect endothelial cell transcription and function. In addition, we will assess the role of microparticle formation in the mechanisms that disrupt the endothelial layer (erosion) and gives rise to a thrombotic event. Analyses will be executed in sex-stratified manner as thrombus on top of stable plaques has been described to be more prevalent in women.

 

Ultimately, this may lead to new mechanisms pointing towards therapy to preserve a healthy endothelium on top on an intact stable plaque.

 

Overall aim:

To unravel which EC-specific mechanisms provoke thrombus on a stable fibrous atherosclerotic lesion, in a sex-specific manner.


Work plan

WP1

WP2

WP3


ENDLESS PREPARE

1. Prioritizing causal genes expressed in endothelium

2. Data harmonization

ENDLESS SELECT

Unravel the functional relevance of selected EC-specific candidate genes for CAD and large artery stroke in endothelial activation, endothelial to
mesenchymal transition (EndoMT), endothelial-leucocyte interaction and EC apoptosis.

ENDLESS FUNCTION

Assess if endogenous microparticles influence the expression of prioritized candidate genes and subsequent
leucocyte and platelet adhesion on an endo-thelial layer and of a stable plaque.