Background
Acute coronary syndromes (ACS) are the most frequent causes leading to myocardial infarction, heart failure, and death. The underlying problem is plaque rupture or erosion, with partial or complete occlusion of a major epicardial coronary artery. Activation of inflammatory pathways may trigger these events. Although progress has been made in prevention and treatment of ACS, its complication rate remains high. This is due to the fact that prevention is not well implemented, triggers of the disease are incompletely understood, and diagnosis is only made once myocardial necrosis has occurred. Importantly, inflammatory mechanisms are not yet incorporated into clinical management. To further improve outcome, patient education should be improved, novel and early diagnostic markers be evaluated and anti-inflammatory strategies developped.

RESEARCH AIMS
The funded subprojects comprise the following research aims (Figure 1):

Figure 1: ACS RESEARCH AIMS OF THE SWISS RESEARCH NETWORK Five major research areas (subproject #) are investigated in a joint effort designed to improve diagnosis, prognosis, therapy, and prevention of patients with ACS.

Aim 1 EDUCATION – improve patient Education after ACS (P-F. Keller, F. Mach, D. Carballo, Geneva; N. Rodondi, R. Auer, Lausanne): This subproject aims to prevent recurrent ACS and its complications by increasing adherence of patients to lifestyle changes and their medications through patient.

Aim 2 BIOMARKERS – identify novel ACS biomarkers (C.M. Matter, R. Klingenberg, Zurich): This subproject will identify novel biomarkers involved in plaque rupture using analyses of systemic and local coronary blood samples, white blood cells within thrombus, and arterial tissue.

Aim 3 PROGNOSIS – test candidate markers suitable for ACS prognosis (W. Maier, L. Altwegg, Zurich): Candidate inflammatory biomarkers such as MRP 8/14 will be evaluated in patients with chest pain seen in the emergency room.

Aim 4 OCT IMAGING – virtual histology of plaques (S.Windecker, L. Raeber, Bern): High-resolution imaging of culprit lesions using optical coherence tomography (OCT) and intravascular ultrasound (IVUS) will identify the morphological features leading to acute coronary narrowing and/or occlusion and determine the role of inflammatory markers.

Aim 5 REPAIR – identify role of progenitor cells after ACS (U. Landmesser, C. Templin, Zurich): The relation between inflammatory pathways and stem/progenitor cell function in patients with ACS will be assessed ex vivo and in vivo and anti-inflammatory therapy analyzed.

EXPERIMENTAL PROTOCOLS
We plan to include over 2000 patients in the Emergency rooms of all 4 University Hospitals (Figure 2) and assess the prognostic impact of candidate biomarkers and of education of patients and caregivers. For the characterization of novel Biomarkers, plaque imaging and progenitor cell function we will recruit patients in the catheterization laboratory.

Figure 2: ORGANIZATION OF THE CONSORTIUM. We plan to include over 2000 patients in the Emergency rooms of all 4 University Hospitals for the subprojects 1 (Prevention, ELIPS) and 3 (Markers of Prognosis) with clinical check and peripheral blood sample. Subprojects 2 (Novel Biomarkers) 4 (OCT Imaging) and 5 (Repair – progenitor cells) will recruit patients in the catheterization laboratory for analyses of plaques via imaging, thrombus aspiration and local blood samples focusing on white blood cells (WBC) and endothelial progenitor cells (EPC).

INTERDISCIPLINARY AND TRANSLATIONAL ASPECTS OF THE SUBPROJECTS
This SNF-project combines experts with backgrounds in various fields of cardiovascular disease in 4 Swiss Universities (Figure 3): Coronary interventions, epidemiology, statistics, prognosis, high-throughput analyses, basic research with foci on pathways of inflammation, stem/progenitor cell biology, molecular plaque imaging. We anticipate that our consortium will foster synergies between the subprojects that will be valuable for science, society and industry.

COLLABORATIONS AT THE UNIVERSITY OF ZURICH
We are grateful for the expert support by collaborators in Zurich that include A. von Eckardstein (Institute for Clinical Chemistry, S. Gay (Center for Experimental Rheumatology), S. P. Hoerstrup (Surgical Research), H. Moch (Institute for Surgical Pathology), Gabriela Senti and G. Zünd (Clinical Trial Center)). This cooperative project is coordinated by T. F. Lüscher and C. M. Matter, Zurich.