Microgravity-induced stress mechanisms in human stem cell-derived cardiomyocytes
Aviseka Acharya,
Harshal Nemade,
Symeon Papadopoulos,
Jürgen Hescheler,
Felix Neumaier,
Toni Schneider,
Krishna Rajendra Prasad,
Khadija Khan,
Ruth Hemmersbach,
Eduardo Gade Gusmao,
Athanasia Mizi,
Argyris Papantonis,
Agapios Sachinidis
Affiliations
Aviseka Acharya
University of Cologne, Faculty of Medicine and University Hospital Cologne, Center for Physiology, Working Group Sachinidis, 50931 Cologne, Germany
Harshal Nemade
University of Cologne, Faculty of Medicine and University Hospital Cologne, Center for Physiology, Working Group Sachinidis, 50931 Cologne, Germany
Symeon Papadopoulos
University of Cologne, Faculty of Medicine and University Hospital Cologne, Center for Physiology, Working Group Sachinidis, 50931 Cologne, Germany
Jürgen Hescheler
University of Cologne, Faculty of Medicine and University Hospital Cologne, Center for Physiology, Working Group Sachinidis, 50931 Cologne, Germany
Felix Neumaier
University of Cologne, Faculty of Medicine and University Hospital Cologne, Center for Physiology, Working Group Sachinidis, 50931 Cologne, Germany
Toni Schneider
University of Cologne, Faculty of Medicine and University Hospital Cologne, Center for Physiology, Working Group Sachinidis, 50931 Cologne, Germany
Krishna Rajendra Prasad
University of Cologne, Faculty of Medicine and University Hospital Cologne, Center for Physiology, Working Group Sachinidis, 50931 Cologne, Germany
Khadija Khan
University of Cologne, Faculty of Medicine and University Hospital Cologne, Center for Physiology, Working Group Sachinidis, 50931 Cologne, Germany
Ruth Hemmersbach
German Aerospace Center, Institute of Aerospace Medicine, Gravitational Biology, Linder Hoehe, 51147 Cologne, Germany
Eduardo Gade Gusmao
Institute of Pathology, University Medical Center Göttingen, 37077 Göttingen, Germany
Athanasia Mizi
Institute of Pathology, University Medical Center Göttingen, 37077 Göttingen, Germany
Argyris Papantonis
Institute of Pathology, University Medical Center Göttingen, 37077 Göttingen, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany
Agapios Sachinidis
University of Cologne, Faculty of Medicine and University Hospital Cologne, Center for Physiology, Working Group Sachinidis, 50931 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany; Corresponding author
Summary: Exposure to outer space microgravity poses a risk for the development of various pathologies including cardiovascular disease. To study this, we derived cardiomyocytes (CMs) from human-induced pluripotent stem cells and exposed them to simulated microgravity (SMG). We combined different “omics” and chromosome conformation capture technologies with live-cell imaging of various transgenic lines to discover that SMG impacts on the contractile velocity and function of CMs via the induction of senescence processes. This is linked to SMG-induced changes of reactive oxygen species (ROS) generation and energy metabolism by mitochondria. Taken together, we uncover a microgravity-controlled axis causing contractile dysfunctions to CMs. Our findings can contribute to the design of preventive and therapeutic strategies against senescence-associated disease.
