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Quantitative proteomics comparing human plaque phenotypes

Objective

Vascular atherosclerotic plaque remodelling leading to rupture is responsible for about half of the total deaths in the European Union. Upon disruption of the atherosclerotic plaque, the highly trombogenic plaque content is exposed to the circulating blood leading to thrombus formation and subsequent occlusion of the artery. When plaque rupture occurs f.e. in a coronary artery this will lead to a myocardial infarction often followed by death.

The mechanisms of plaque remodelling leading to destabilization and rupture are poorly understood. Since appropriate animal models for plaque rupture are lacking, we use as a starting point a large number (~600) of well characterized carotid endarterectomy specimen from patients that are well documented and undergo a follow up. We combine this Dutch tissue bank with state of the art proteomics approaches present in Singapore.

This combination will use the classical approach to screen for proteins that differ between stable fibrous and unstable inflammatory plaques and between stable and ruptured plaque (Objective 1). Next to this approach, we will screen for proteins that differ between for proteins that differ between patients that had a cardiovascular event and control patients, an approach that can redefine the definition of the vulnerable plaque (Objective 2). The differential expression of the proteins will be validated in a large population allowing correction for confounding (Objective 3).

After the proteomics approach and return to the Netherlands, we will investigate t he role of the differentially expressed proteins as a blood marker and its function. The research performed in the frame of this project will increase the global understanding of atherosclerosis and largely impact the overall management of this pathology as well as the development of novel therapeutic strategies and biomarkers.

Call for proposal

FP6-2004-MOBILITY-6
See other projects for this call

Funding Scheme

OIF - Marie Curie actions-Outgoing International Fellowships

Coordinator

INTERUNIVERSITY CARDIOLOGY INSTITUTE OF THE NETHERLANDS/ROYAL DUTCH ACADEMY OF ART AND SCIENCES
Address
Catherijnesingel 52
Utrecht
Netherlands

Participants (1)

GENOME INSTITUTE SINGAPORE
Singapore
Address
Genome #02-01, 60 Biopolis Street
Singapore