Arterial thrombosis caused by atherosclerosis in the coronary arteries is the most frequent cause of cardiovascular death and disability in Denmark and worldwide. The disease is caused by circulating cholesterol-rich lipoproteins, which in concert with hypertension, diabetes, smoking and familiar disposition, lead to atherosclerotic plaques in the inner layer of major arteries. Plaques develop slowly and often without symptoms, but may suddenly give rise to life-threatening platelet-dependent thrombosis (acute coronary syndrome) necessitating rapid intervention with PCI and anti-thrombotic drugs to restore blood flow to the myocardium.

Thrombosis

Platelets are key players in arterial thrombus formation. Antiplatelet agents like aspirin and ADP-blockers effectively inhibit platelet aggregation thus reducing the risk of thrombotic events. However, some patients do not respond adequately to these drugs (Grove et al. Future Cardiol. 2009), and platelet function testing serves as a promising tool to evaluate their antiplatelet effect (Grove et al. Thromb Haemost. 2010).
A reduced antiplatelet effect of aspirin has been demonstrated in coronary artery disease patients with type 2 diabetes mellitus (Mortensen et al. Thromb Res. 2010) or previous stent thrombosis (Würtz et al. JACC Cardiovasc Interv. 2010). Interestingly, patients with acute coronary syndromes have an increased platelet turnover (Grove et al. Thromb Haemost. 2009), which may partly explain a reduced antiplatelet effect of aspirin (Grove et al. J Thromb Haemost. 2011). Ongoing research projects are investigating mechanisms, treatment efficacy and survival in these patients.

Vulnerable Plaques

Through the description of plaque rupture as the most common cause of coronary thrombosis in the early 1990s (Falk E. Circulation. 1995), it has become clear that only a small subgroup of atherosclerotic plaques in a patient actually poses a risk. Their development, detection, and treatment are a major focus of ongoing research (Thim et al. Circ Cardiovasc Imaging. 2010), as is the identification of peopleharboring such high-risk (vulnerable) lesions (Muntendam et al. Am Heart J. 2010).

Experimental Pathology

Acquiring knowledge about disease mechanisms requires experiments in animal models. Our team uses mouse models to understand central mechanisms in atherogenesis and is developing novel atherosclerosis models in transgenic minipigs for preclinical research (DAGMAR). In recent years, special emphasis has been on cell tracking where we have refuted a number of contemporary theories of progenitor cell involvement in atherosclerosis (Hagensen et al. Circulation. 2010).

Contacts

Sanne Bøjet Larsen, MD, PhD -student, sanne.larsen@ki.au.dk
Søs Bousgaard Mortensen, MD, PhD-student, sosbm@dadlnet.dk
Kristina Grønborg Laut, MPH, PhD-student, kristina@laut.dk
Peter Rubak, Master of Health Science., PhD-student, peterrubak@gmail.com
Morten Würtz, MD, PhD-student, morten.wurtz@ki.au.dk
Erik Lerkevang Grove,MD, PhD, erikgrove@dadlnet.dk
Vivi Bo Mogensen, laboratory assistant, vivi.mogensen@skejby.rm.dk
Pia Hansen, secretary, piahasen@rm.dk
Anne-Mette Hvas, MD, PhD, annehvas@rm.dk
Steen Dalby Kristensen, MD, DMSci, steendk@dadlnet.dk
Martin Bødtker Mortensen, PhD-student, martin.bodtker.mortensen@ki.au.dk
Rozh Hussein Al-Mashhadi, MD, PhD-student., r.al-mashhadi@ki.au.dk
Mette Hagensen, MSc, post.doc., mette.hagensen@ki.au.dk
Lisa Maria Røge, technician, lmr@ki.au.dk
Dorte Wilhardt Jørgensen, technician, dwj@ki.au.dk
Jacob Fog Bentzon, associate professor, jben@ki.au.dk
Erling Falk, professor, erling.falk@ki.au.dk