Principal Investigator: T. F. Lüscher

Subproject 1

Optimize prevention after ACS by improving caregiver and patient education


(P-F. Keller, D. Carballo, S. Carballo, Geneva)

(Perneger, Rodondi, Geneva)

This subproject aims to prevent recurrent ACS and its complications by increasing adherence of patients to lifestyle changes and their medications through patient education and to increase prescription rates of evidence-based medications and counseling practice of health care providers.

Subproject 2

Discover novel genomic biomarkers of ACS


(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 obtained in the catheterization laboratory, in the operation theater or at autopsy, respectively.

Inflammation and acute coronary syndromes (ACS)–a clinical research network funded by the Swiss National Science Foundation
CM Mattera, R Klingenbergb, C Templinb, L … – Kardiovaskuläre …, 2010 –
In February 2009, the Universities of Bern, Geneva, Lausanne and Zurich joined forces for the
project “In- flammation and acute coronary syndromes (ACS) – Novel strategies for prevention
and clinical manage- ment”. This clinical research program underwent peer review and

Treating inflammation in atherosclerotic cardiovascular disease: emerging therapies

R Klingenberg, GK Hansson – European heart journal, 2009 – Eur Soc Cardiology
Atherosclerosis constitutes the underlying disease to the clinical manifestations of myocardial
infarction, stroke, and gangrene. Despite the success of statins, prevention of clinical events
of atherosclerosis remains a major challenge in current-day cardiology. Research into the

Imaging of the unstable plaque: how far have we got?
CM Matter, M Stuber, M Nahrendorf – European heart journal, 2009 – Eur Soc Cardiology
Rupture of unstable plaques may lead to myocardial infarction or stroke and is the leading cause
of morbidity and mortality in western countries. Thus, there is a clear need for identifying these
vulnerable plaques before the rupture occurs. Atherosclerotic plaques are a challenging

Molecular imaging of atherosclerotic plaques using a human antibody against the extra-domain B
CM Matter, PK Schuler, P Alessi, P Meier, R … – Circulation …, 2004 –
Current imaging modalities of human atherosclerosis, such as angiography, ultrasound, and
computed tomography, visualize plaque morphology. However, methods that provide insight
into plaque biology using molecular tools are still insufficient. The extradomain B (ED-B)

PARP1 is required for adhesion molecule expression in
T Von Lukowicz, PO Hassa, C … – Cardiovascular …, 2008 –
Methods and results: In order to test the role of PARP in atherogenesis, we applied chronic pharmacological
PARP inhibition or genetic PARP1 deletion in atherosclerosis-prone apolipoprotein E-deficient
mice and measured plaque formation, adhesion molecules, and features of plaque


Intranasal immunization with an apolipoprotein B-100 fusion protein induces antigen-specific regulatory T cells and reduces atherosclerosis.

Klingenberg R, Lebens M, Hermansson A, Fredrikson GN, Strodthoff D, Rudling M, Ketelhuth DF, Gerdes N, Holmgren J, Nilsson J, Hansson GK.

Arterioscler Thromb Vasc Biol. 2010 May;30(5):946-52.

Sphingosine-1-phosphate analogue FTY720 causes lymphocyte redistribution and hypercholesterolemia in ApoE-deficient mice.

Klingenberg R, Nofer JR, Rudling M, Bea F, Blessing E, Preusch M, Grone HJ, Katus HA, Hansson GK, Dengler TJ.

Arterioscler Thromb Vasc Biol. 2007 Nov;27(11):2392-9. Epub 2007 Aug 30.

Subproject 3

Evaluate novel diagnostic and prognostic biomarkers

(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, including those with ACS who will be followed for 12 months to examine the prognostic impact of these markers.

Subproject 4

Visualize the vulnerable plaque using optical coherence tomography (OCT)

(S. Windecker, L. Räber, Bern)

High-resolution imaging of culprit lesions of ACS using OCT and intravascular ultrasound (IVUS) will identify the morphological features (i.e. plaque rupture, erosion, hemorrhage, calcified nodules) leading to acute coronary narrowing and/or occlusion and determine the role of inflammatory markers.

Räber L, Windecker S.

Cardiovasc Ther. 2010 Mar 27. [Epub ahead of print]
Räber L, Jüni P, Löffel L, Wandel S, Cook S, Wenaweser P, Togni M, Vogel R, Seiler C, Eberli F, Lüscher T, Meier B, Windecker S.

Subproject 5

Characterize the role of inflammation for progenitor/stem cell-mediated repair after ACS

(U. Landmesser, C. Templin, Zurich)

Based on our own data, we will investigate the relation between inflammatory pathways and stem/progenitor cell function in patients with ACS ex vivo and in vivo. We will further analyze the effect of anti-inflammatory therapy on stem/progenitor cell-mediated cardiac repair.


Arrhythmia Susceptibility in Mice after Therapy with beta-Catenin-Transduced Hematopoietic Progenitor Cells after Myocardial Ischemia/Reperfusion.

Gardiwal A, Reissmann LM, Kotlarz D, Oswald H, Korte T, Landmesser U, Klein G, Templin C.

Cardiology. 2009 Jul 15;114(3):199-207. [Epub ahead of print]

Bone marrow cell therapy after myocardial infarction. What should we select?

Landmesser U.

Eur Heart J. 2009 Jun;30(11):1310-2. Epub 2009 May 7. No abstract available.

Ex vivo expanded hematopoietic progenitor cells improve cardiac function after myocardial infarction: role of beta-catenin transduction and cell dose.

Templin C, Kotlarz D, Faulhaber J, Schnabel S, Grote K, Salguero G, Luchtefeld M, Hiller KH, Jakob P, Naim HY, Schieffer B, Hilfiker-Kleiner D, Landmesser U, Limbourg FP, Drexler H.

J Mol Cell Cardiol. 2008 Sep;45(3):394-403. Epub 2008 Jul 11.

Oxidant stress impairs in vivo reendothelialization capacity of endothelial progenitor cells from patients with type 2 diabetes mellitus: restoration by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone.

Sorrentino SA, Bahlmann FH, Besler C, Müller M, Schulz S, Kirchhoff N, Doerries C, Horváth T, Limbourg A, Limbourg F, Fliser D, Haller H, Drexler H, Landmesser U.

Circulation. 2007 Jul 10;116(2):163-73. Epub 2007 Jun 25.

Transcoronary delivery of bone marrow cells to the infarcted murine myocardium: feasibility, cellular kinetics, and improvement in cardiac function.

Templin C, Kotlarz D, Marquart F, Faulhaber J, Brendecke V, Schaefer A, Tsikas D, Bonda T, Hilfiker-Kleiner D, Ohl L, Naim HY, Foerster R, Drexler H, Limbourg FP.

Basic Res Cardiol. 2006 Jul;101(4):301-10. Epub 2006 May 16.


J Am Coll Cardiol. 2010 Mar 23;55(12):1178-88