The cardiac matrix, a vital regulator of inflammation during viral myocarditis.

The collagen matrix of the heart is essential for maintenance of structural
and functional integrity of the heart. Matrix metalloproteinases (MMPs),
plasminogen activators (PAs) and their respective inhibitors (TIMP/PAI) are
strongly involved in remodelling of the cardiac matrix, thereby
influencing cardiac function and geometry during ischemic and dilated
cardiomyopathy.
The present project intends to investigate the unknown role of PA/MMP
systems in cardiac inflammation, injury, dilatation and dysfunction during
acute/chronic cardiac allograft rejection and during viral myocarditis.
First, a murine model of human Coxsackie-B3 virus- induced myocarditis and
murine cardiac allograft transplantation will be performed in PA/MMP and
PAI-1/TIMP-1-gene inactivated mice, after PAI-1/TIMP-1-gene overexpression
or during administration of synthetic MMP-inhibitors in mice. To move to
human disease, prospective and retrospective studies will be performed in
patients with viral myocarditis and cardiac allograft transplantation,
investigating PA/MMPs and their inhibitors in biopsies and serial blood
samples, in correlation with haemodynamic and structural measurements.

Keywords:Myocarditis

Disciplines:Cardiac and vascular medicine