Unravelling Mechanotransduction Pathways in the Heart

Non-FAU Project


Project Details

Project leader:
Prof. Dr. Dr. Oliver Friedrich


Contributing FAU Organisations:
Lehrstuhl für Medizinische Biotechnologie

Start date: 01/01/2016
End date: 31/12/2019


Abstract (technical / expert description):

Pathological myocardial hypertrophy is a maladaptive process occurring in response to an increased cardiac workload [1, 2]. Left ventricular hypertrophy (LVH) is the single most important predictor of premature cardiovascular death in the Framingham risk assessment. In addition, it is a major risk factor for various cardiac arrhythmias, such as atrial fibrillation, the most common significant cardiac rhythm disturbance. The members of a TRPC subfamily of transient receptor potential (TRP)-type ion channels, TRPC3 and TRPC6, have been implicated in development of the cardiac hypertrophy and progression to heart failure [3, 4]. This project will test the hypothesis that cardiac pressure-overload instigates a stretch-mediated up-regulation of cardiac TRPC3 and TRPC6 ion channels, leading to Ca2+ entry, which activates a signaling cascade involving Ca2+/calmodulin-dependent protein kinase II (CaMKII)/histone deacetylase 4 (HDAC4)/myocyte enhancer factor-2 (MEF2) to induce hypertrophy and associated arrhythmias.


Publications

Friedrich, O., Merten, A.-L., Schneidereit, D., Guo, Y., Schürmann, S., & Martinac, B. (2019). Stretch in Focus: 2D Inplane Cell Stretch Systems for Studies of Cardiac Mechano-Signaling. Frontiers in Bioengineering and Biotechnology, 7. https://dx.doi.org/10.3389/fbioe.2019.00055
Friedrich, O., Schneidereit, D., Nikolaev, Y.A., Nikolova-Krstevski, V., Schürmann, S., Wirth-Hücking, A.,... Martinac, B. (2017). Adding dimension to cellular mechanotransduction: Advances in biomedical engineering of multiaxial cell-stretch systems and their application to cardiovascular biomechanics and mechano-signaling. Progress in biophysics and molecular biology. https://dx.doi.org/10.1016/j.pbiomolbio.2017.06.011
Schürmann, S., Wagner, S., Herlitze, S., Fischer, C., Gumbrecht, S., Wirth-Hücking, A.,... Friedrich, O. (2016). The IsoStretcher: An isotropic cell stretch device to study mechanical biosensor pathways in living cells. Biosensors and Bioelectronics, 81, 363-72. https://dx.doi.org/10.1016/j.bios.2016.03.015

Last updated on 2019-28-06 at 22:44