Klinikstr. 6-8, 97070 Würzburg
Research foci (and basic equipment-based research projects):
1. Disease manifestation and management in congestive heart failure.
2. Pathophysiology and pathogenesis of idiopathic dilated cardiomyopathy.
3. Molecular biological aspects of the pathogenesis of CHF.
4. Pathophysiology, pathogenesis and means of therapeutic interventions in complications after cardiac transplantation.
5. Hormone replacement therapy in postmenopausal women.
6. Noninvasive cardiac imaging with ultrasound at rest and during stress combined with ultrasound contras.
ad 1. Goal of this project is the establishment of a research and disease management programme for patients with congestive heart failure termed „Interdisciplinary network CHF“ (INH) at the Herz- und Kreislaufzentrum, University of Würzburg to be located at the Medizinische Universitätspoliklinik. This is realized by implementation of a specialized programme for patient management and education, a clinical data base for epidemiological and health care research and a systematic collection of blood for molecular genetic research from all patients included in the programme. (no results available so far)
ad 2. In about one third of patients with dilated cardiomyopathy (DCM) we were able to detect stimulating auto-antibodies directed against the second extracellular loop of the beta1-adrenergic receptor (II.EC-loop ß1-AR). Left ventricular function was significantly more reduced in ß1-AR antibody-positive compared with antibody-negative DCM patients. To further analyze the pathogenetical relevance of such receptor-antibodies we attempted to generate a model for ß1-AR targeted immune cardiomyopathy in the rat (100% sequence identity II.EC-loop ß1-AR human/rat): in an inbred rat strain we were able to induce a cardiomyopathic phenotype both (1) by immunization of the animals against the II.EC-loop of the ß1-AR (indirect evidence) and, subsequently, also (2) by intravenous transfer of antibody-containing sera from immunized rats to healthy rats of the same strain (direct evidence - following Koch's classical postulates of auto-immune diseases) thus confirming the pathogenetic concept of receptor-targeted autoimmune cardiomyopathy as a possible cause of DCM.
ad 3. It was shown in an animal model of congestive heart failure that besides classical proinflammatory cytokines, such as TNF-alpha, also chemokines and their corresponding receptors are expressed.Monocyte chemoattractant protein-1(MCP-1) is a main example of the class of CC-chemokines. The expression of MCP-1 in heart failure was shown in infiltrating leucocytes, endothelium, vascular smooth muscle cells and in cardiomyocytes. Further we it was shown that angiotensin receptor antagonism with teveten reduced MCP-1 expression, which is paralleled by reduced mortality and improved cardiac hemodynamics. A further related research project was designed to clarify the role of p38 MAPK in cardiac hypertrophy and decompensation. The mechanims behind the therapeutic effect of MAPK-inhibitors were studied.
ad 3. This project consists of clinical and experimental studies evaluating chronic complications after cardiac transplantation and progressive renal failure after cardiac transplantation. (no results available so far)
ad 4. This project consists of clinical and experimental studies evaluating chronic complications after cardiac transplantation and progressive renal failure after cardiac transplantation.
ad 5. Postmenopausal hormone replacement therapy (HRT) is associated with low cardiovascular morbidity and mortality in epidemiological studies and has been widely recommended, even in primary prevention situations. However, data from 2 randomized trials were discouraging . This project aims at characterizing the effect of a estradiol-based HRT on a variety of surrogate markers of atherosclerosis and bone metabolism in healthy postmenopausal women with subclinical athersclerosis.
ad 6. With new ultrasound contrast agents and specific machine settings and properties an improvement in echocardiographic image quality and the direct messurement of myocardial perfusion is yielded. Furthermore, using tissue velocity imaging, wall motion and deformation (strain) can be quantified. Several ongoing studies examine the potential diagnostic benefit of these new imaging modalities.