Klapproth Group
Molecular pathophysiology of the heart
Despite lege artis treatment with ACE inhibitors and/or beta-adrenoceptor blockers, chronic heart failure, e.g. as a result of a heart attack, remains a major clinical challenge. In addition to electrophysiological remodelling, fibrotic remodelling of the extracellular matrix is of central importance during heart failure pathogenesis. This fibrotic remodelling is not only determined by the activation of collagen-producing cardiac fibroblasts. The release of growth factors and specialized matrix remodelling enzymes, which e.g. promote scar formation as a result of the infarct, is also of crucial importance. On the one hand, these processes considerably reduce the pumping capacity of the heart, but on the other hand they offer concrete starting points for a targeted therapy. The aim of our group is to contribute to a better understanding of the underlying signalling mechanisms in order to realize such novel treatment strategies. Our main focus is on the investigation of proteolytic ECM processing enzymes - ADAMs (A disintegrin metalloprotease) and beta-adrenergic signalling cascades.
Methods
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cardiomyocyte specific ADAM10, ADRB1, ADRB2, ADRB3 knockout mice
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induced pluripotent stem cell technology (iPSCs)
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CrisprCas9-ediated gen knockout
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SDS-PAGE und Western blotting
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analysis of signaltransduction
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analysis of protein interactions
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microscopy
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histology
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mass spectrometrie (in cooperation)
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Omics (in cooperation)