Our institute investigates the role of cAMP and cGMP in heart failure. These ubiquitous second messengers show both negative and protective effects in cardiomyocytes. The outcome of their signals eventually depends on the subcellular compartments where cAMP and cGMP exert their action. For example, beta2-adrenergic receptors localized in the T-tubules of healthy cardiomyocytes can activate cardioprotective mechanisms, whereas in failing myocytes, the same receptors change their location and may exert detrimental effects. We use highly sensitive biosensors and new imaging techniques such as fluorescence resonance energy transfer (FRET) and scanning ion conductance microscopy (SICM) to visualize cAMP and cGMP gradients with high temporal and spatial precision in various subcellular areas of cardiomyocytes. Combined with the analysis of membrane ultrastructure in healthy and failing cells, this information should shed light on the molecular mechanisms of heart failure and help identify new therapeutic strategies.

Our work is supported by the Gertraud und Heinz-Rose Foundation, German Center of Cardiovascular Research (DZHK) and the German Research Foundation (DFG)