Project: Atherosclerotic plaque erosion leading to thrombus formation. The role of extracellular vesicles in ENDotheliaL transdiffErentiation, apoptoSiS and leucocyte and platelet adhesion.

Acronym	ENDLESS (Reference Number: 6. JTC-2017_49)
Project Topic	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.
Network	ERA-CVD
Call	Joint Transnational Call for Proposals 2017: Mechanisms of early atherosclerosis and/or plaque instability in Coronary Artery Disease

Project partner

Number	Name	Role	Country
1	University Medical Center Utrecht	Coordinator	Netherlands
2	INSERM	Partner	France
3	Charite University medicine	Partner	Germany
4	Hacettepe University	Partner	Türkiye