TY - GEN A1 - Münch, Juliane A1 - Abdelilah-Seyfried, Salim T1 - Sensing and Responding of Cardiomyocytes to Changes of Tissue Stiffness in the Diseased Heart T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Cardiomyocytes are permanently exposed to mechanical stimulation due to cardiac contractility. Passive myocardial stiffness is a crucial factor, which defines the physiological ventricular compliance and volume of diastolic filling with blood. Heart diseases often present with increased myocardial stiffness, for instance when fibrotic changes modify the composition of the cardiac extracellular matrix (ECM). Consequently, the ventricle loses its compliance, and the diastolic blood volume is reduced. Recent advances in the field of cardiac mechanobiology revealed that disease-related environmental stiffness changes cause severe alterations in cardiomyocyte cellular behavior and function. Here, we review the molecular mechanotransduction pathways that enable cardiomyocytes to sense stiffness changes and translate those into an altered gene expression. We will also summarize current knowledge about when myocardial stiffness increases in the diseased heart. Sophisticated in vitro studies revealed functional changes, when cardiomyocytes faced a stiffer matrix. Finally, we will highlight recent studies that described modulations of cardiac stiffness and thus myocardial performance in vivo. Mechanobiology research is just at the cusp of systematic investigations related to mechanical changes in the diseased heart but what is known already makes way for new therapeutic approaches in regenerative biology. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1234 KW - mechanobiology KW - tissue stiffness KW - cardiomyocyte KW - heart regeneration KW - titin KW - collagen KW - agrin KW - extracellular matrix Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-545805 SN - 1866-8372 ER - TY - JOUR A1 - Münch, Juliane A1 - Abdelilah-Seyfried, Salim T1 - Sensing and responding of cardiomyocytes to changes of tissue stiffness in the diseased heart JF - Frontiers in cell developmental biology N2 - Cardiomyocytes are permanently exposed to mechanical stimulation due to cardiac contractility. Passive myocardial stiffness is a crucial factor, which defines the physiological ventricular compliance and volume of diastolic filling with blood. Heart diseases often present with increased myocardial stiffness, for instance when fibrotic changes modify the composition of the cardiac extracellular matrix (ECM). Consequently, the ventricle loses its compliance, and the diastolic blood volume is reduced. Recent advances in the field of cardiac mechanobiology revealed that disease-related environmental stiffness changes cause severe alterations in cardiomyocyte cellular behavior and function. Here, we review the molecular mechanotransduction pathways that enable cardiomyocytes to sense stiffness changes and translate those into an altered gene expression. We will also summarize current knowledge about when myocardial stiffness increases in the diseased heart. Sophisticated in vitro studies revealed functional changes, when cardiomyocytes faced a stiffer matrix. Finally, we will highlight recent studies that described modulations of cardiac stiffness and thus myocardial performance in vivo. Mechanobiology research is just at the cusp of systematic investigations related to mechanical changes in the diseased heart but what is known already makes way for new therapeutic approaches in regenerative biology. KW - mechanobiology KW - tissue stiffness KW - cardiomyocyte KW - heart regeneration KW - titin KW - collagen KW - agrin KW - extracellular matrix Y1 - 2020 U6 - https://doi.org/10.3389/fcell.2021.642840 SN - 2296-634X VL - 9 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - MacGrogan, Donal A1 - Münch, Juliane A1 - de la Pompa, José Luis T1 - Notch and interacting signalling pathways in cardiac development, disease, and regeneration JF - Nature Reviews Cardiology N2 - Cardiogenesis is a complex developmental process involving multiple overlapping stages of cell fate specification, proliferation, differentiation, and morphogenesis. Precise spatiotemporal coordination between the different cardiogenic processes is ensured by intercellular signalling crosstalk and tissue-tissue interactions. Notch is an intercellular signalling pathway crucial for cell fate decisions during multicellular organismal development and is aptly positioned to coordinate the complex signalling crosstalk required for progressive cell lineage restriction during cardiogenesis. In this Review, we describe the role of Notch signalling and the crosstalk with other signalling pathways during the differentiation and patterning of the different cardiac tissues and in cardiac valve and ventricular chamber development. We examine how perturbation of Notch signalling activity is linked to congenital heart diseases affecting the neonate and adult, and discuss studies that shed light on the role of Notch signalling in heart regeneration and repair after injury. KW - Cardiac regeneration KW - Cell signalling KW - Congenital heart defects KW - Heart development Y1 - 2018 U6 - https://doi.org/10.1038/s41569-018-0100-2 SN - 1759-5002 SN - 1759-5010 VL - 15 IS - 11 SP - 685 EP - 704 PB - Nature Publ. Group CY - New York ER - TY - JOUR A1 - Andrés-Delgado, Laura A1 - Ernst, Alexander A1 - Galardi-Castilla, María A1 - Bazaga, David A1 - Peralta, Marina A1 - Münch, Juliane A1 - Gonzalez-Rosa, Juan M. A1 - Marques, Inês A1 - Tessadori, Federico A1 - de la Pompa, José Luis A1 - Vermot, Julien A1 - Mercader, Nadia T1 - Actin dynamics and the Bmp pathway drive apical extrusion of proepicardial cells JF - Development : Company of Biologists N2 - The epicardium, the outer mesothelial layer enclosing the myocardium, plays key roles in heart development and regeneration. During embryogenesis, the epicardium arises from the proepicardium (PE), a cell cluster that appears in the dorsal pericardium (DP) close to the venous pole of the heart. Little is known about how the PE emerges from the pericardial mesothelium. Using a zebrafish model and a combination of genetic tools, pharmacological agents and quantitative in vivo imaging, we reveal that a coordinated collective movement of DP cells drives PE formation. We found that Bmp signaling and the actomyosin cytoskeleton promote constriction of the DP, which enables PE cells to extrude apically. We provide evidence that cell extrusion, which has been described in the elimination of unfit cells from epithelia and the emergence of hematopoietic stem cells, is also a mechanism for PE cells to exit an organized mesothelium and fulfil their developmental fate to form a new tissue layer, the epicardium. KW - Actomyosin KW - Bmp KW - Cell extrusion KW - Proepicardium KW - Zebrafish KW - Heart development Y1 - 2019 U6 - https://doi.org/10.1242/dev.174961 SN - 0950-1991 SN - 1477-9129 VL - 146 IS - 13 PB - The Company of Biologists Ltd CY - Cambridge ER -