Sensory Neurons Release Cardioprotective Factors in an In Vitro Ischemia Model

Autor(en)
Clara Hoebart, Attila Kiss, Bruno K. Podesser, Ammar Tahir, Michael J.M. Fischer, Stefan Heber
Abstrakt

Sensory neurons densely innervate the myocardium. The role of their sensing and response to acute and prolonged ischemia is largely unclear. In a cellular model of ischemia-reperfusion injury, the presence of sensory neurons increases cardiomyocyte survival. Here, after the exclusion of classical neurotransmitter release, and measurement of cytokine release, we modified the experiment from a direct co-culture of primary murine cardiomyocytes and sensory neurons to a transfer of the supernatant. Sensory neurons were exposed to ischemia and the resulting conditioned supernatant was transferred onto cardiomyocytes. This approach largely increased the tolerance of cardiomyocytes to ischemia and reperfusion. Towards the identification of the mechanism, it was demonstrated that after ten-fold dilution, the conditioned solution lost its protective effect. The effect remained after removal of extracellular vesicles by ultracentrifugation, and was not affected by exposure to protease activity, and fractionation pointed towards a hydrophilic agent. Solutions conditioned by HEK293t cells or 3T3 fibroblasts also increase cardiomyocyte survival, but to a lower degree. A metabolomic search identified 64 at least two-fold changed metabolites and lipids. Many of these could be identified and are involved in essential cellular functions. In the presented model for ischemia-reperfusion, sensory neurons secrete one or more cardioprotective substances that can improve cardiomyocyte survival.

Organisation(en)
Department für Pharmazeutische Wissenschaften, Institut für Analytische Chemie, Institut für Geographie und Regionalforschung, Institut für Sport- und Bewegungswissenschaft
Externe Organisation(en)
Medizinische Universität Wien, Center for Biomedical Research and Translational Surgery
Journal
Biomedicines
Band
12
ISSN
2227-9059
DOI
https://doi.org/10.3390/biomedicines12081856
Publikationsdatum
08-2024
Peer-reviewed
Ja
ÖFOS 2012
301204 Pharmakognosie
Schlagwörter
ASJC Scopus Sachgebiete
Medicine (miscellaneous), Allgemeine Biochemie, Genetik und Molekularbiologie
Link zum Portal
https://ucrisportal.univie.ac.at/de/publications/3b71dc39-e2a7-49fa-83c0-7b2e7ddf73e8