Primary cardiomyopathy involves the most common cause of sudden cardiac death in young people. The onset of this cardiac disease ranges between 20 and 50 years of age. Primary cardiomyopathies are caused by mutations in genes encoding for sarcomeric proteins. At present there is no specific medical treatment since the exact mechanisms underlying cardiac dysfunction in primary cardiomyopathy are still unknown.
As a first step in understanding the pathophysiology of primary cardiomyopathy, functional assays and proteomics will be performed in human myocardium to reveal sarcomeric changes specific for primary cardiomyopathies. Targeted protein exchange experiments will be used to proof causality between the mutant protein and sarcomeric dysfunction. Longitudinal studies in transgenic mice models will disentangle adaptive from maladaptive protein changes in the initiation and progression of cardiomyopathy. To determine the consequences of sarcomeric alterations, in vitro data will be correlated with in vivo myocardial properties of the heart. The present study will reveal sarcomeric targets for treatment strategies to prevent the onset of cardiomyopathy in mutation carriers and delay or even reverse cardiac dysfunction in patients with manifest cardiomyopathy.
This 5-year project (2011-2016; 800.000 euros) will be executed in the department of Physiology.