Research Report 2010 - MDC

Rainer DietzStructure of the GroupGroup LeaderProf. Dr. Rainer DietzScientistsDr. Florian BlaschkePD Dr. Ralf DechendDr. Stefan DonathDr. Jens FielitzDr. Robert FischerDr. Jan MontiPD Dr. Cemil ÖzcelikDr. Laura ZelarayánClinical CardiologyThe main topic of the group is to address the molecular signaling pathways leading to heartfailure. Heart failure, a highly heterogenous disease, is characterized by a symptomcomplex of congestion and exertional fatigue. Heart failure is mainly caused by coronaryartery disease/myocardial infarction, arterial hypertension, dilated and hypertrophiccardiomyopathies, and inflammatory heart disease. In a translational approach new animalmodels have been established mimicking those human cardiovascular disorders and theireffects. Detailed phenotyping of those heart failure models has revealed new insights intodisease development and adaptive compensatory pathways prior to the onset of heart failurewhich may lead to new preventive and therapeutic strategies.BackgroundAlthough great progress has been achieved in the treatmentof heart failure, it remains a leading cause ofdeath and disability throughout the world and prevalenceand incidence increase year-by-year. Heart homeostasisis regulated by apoptosis, cardiomyocyte hypertrophyand myocardial regeneration determining thehearts ability to response to pathologic loads. The balancebetween cardiomyoycte survival and apoptoticpathways as well as heart regeneration versus deleteriouscardiac remodelling appear to be key determinantsof the transition from heart hypertrophy to ventriculardilatation.Complex Genetics of Hypertension andHeart FailureJan Monti, Jens ButtgereitIn humans, hypertension associated with sustained cardiachypertrophy represents one of the most commoncauses of heart failure. Starting from high blood pressure,the pathophysiological cardiac remodelling cascadeproceeds to left ventricular hypertrophy as a primarilyadaptive process. Later on, left ventricular dilatation,decreased systolic function, and cardiac arrhythmiascan occur in some patients, whereas others retainstable systolic function without clinical signs of heartfailure.Heart failure is thought to result from complex interactionsbetween genetic susceptibility and lifestyle/environmental factors. In close collaboration withNorbert Hübner, Jan Monti aimed to identify gene variantsunderlying heart failure in the spontaneouslyhypertensive heart failure (SHHF) rat. They generatedexperimental evidence that genetic variance in theEphx2 (soluble epoxide hydrolase) gene facilitates progressionfrom hypertension and cardiac hypertrophy toheart failure in that rat model. The demonstratedcausative impact for Ephx2 in the complex initiation ofheart failure in rats and mice inaugurate Ephx2 as anew heart failure treatment avenue.Hypertension and Heart FailureRalf Dechend, Florian Herse, Katrin WenzelIn addition to genetic predisposition the subgroup ofRalf Dechend examined the relevance of “agonistic”autoantibodies directed against the α1-adrenergicreceptor in patients with refractory hypertension.Almost half of them displayed α1-autoantibodies.Interestingly, the removal of the α1-autoantibodies byimmunoabsorption significantly reduced blood pressureduring the observed follow-up phase of 180 days.By this innovative therapeutic approach Ralf Dechend38 Cardiovascular and Metabolic Disease Research