title: Argon Induces Protective Effects in Cardiomyocytes during the Second Window of Preconditioning.
abstract: Increasing evidence indicates that argon has organoprotective properties. So far, the underlying mechanisms remain poorly understood. Therefore, we investigated the effect of argon preconditioning in cardiomyocytes within the first and second window of preconditioning. Primary isolated cardiomyocytes from neonatal rats were subjected to 50% argon for 1 h, and subsequently exposed to a sublethal dosage of hypoxia (<1% O₂) for 5 h either within the first (0-3 h) or second window (24-48 h) of preconditioning. Subsequently, the cell viability and proliferation was measured. The argon-induced effects were assessed by evaluation of mRNA and protein expression after preconditioning. Argon preconditioning did not show any cardioprotective effects in the early window of preconditioning, whereas it leads to a significant increase of cell viability 24 h after preconditioning compared to untreated cells (p = 0.015) independent of proliferation. Argon-preconditioning significantly increased the mRNA expression of heat shock protein (HSP) B1 (HSP27) (p = 0.048), superoxide dismutase 2 (SOD2) (p = 0.001), vascular endothelial growth factor (VEGF) (p < 0.001) and inducible nitric oxide synthase (iNOS) (p = 0.001). No difference was found with respect to activation of pro-survival kinases in the early and late window of preconditioning. The findings provide the first evidence of argon-induced effects on the survival of cardiomyocytes during the second window of preconditioning, which may be mediated through the induction of HSP27, SOD2, VEGF and iNOS.
authors.affiliation: Department of Thoracic &amp; Cardiovascular Surgery, University Hospital RWTH, 52074 Aachen, Germany. Britta.Mayer@rwth-aachen.de.
authors.forename: Britta
authors.initials: B
authors.lastname: Mayer
authors.affiliation: Department of Thoracic &amp; Cardiovascular Surgery, University Hospital RWTH, 52074 Aachen, Germany. jsoppert@ukaachen.de.
authors.forename: Josefin
authors.initials: J
authors.lastname: Soppert
authors.affiliation: Department of Thoracic &amp; Cardiovascular Surgery, University Hospital RWTH, 52074 Aachen, Germany. skraemer@ukaachen.de.
authors.forename: Sandra
authors.initials: S
authors.lastname: Kraemer
authors.affiliation: Department of Thoracic &amp; Cardiovascular Surgery, University Hospital RWTH, 52074 Aachen, Germany. Sabrina.Schemmel@rwth-aachen.de.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Schemmel
authors.affiliation: Department of Thoracic &amp; Cardiovascular Surgery, University Hospital RWTH, 52074 Aachen, Germany. cbeckers@ukaachen.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Beckers
authors.affiliation: Department of Anesthesiology, University Hospital RWTH, 52074 Aachen, Germany. cbleilevens@ukaachen.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Bleilevens
authors.affiliation: Department of Anesthesiology, University Hospital RWTH, 52074 Aachen, Germany. rrossaint@ukaachen.de.
authors.forename: Rolf
authors.initials: R
authors.lastname: Rossaint
authors.affiliation: Department of Anesthesiology, University Hospital RWTH, 52074 Aachen, Germany. mcoburn@ukaachen.de.
authors.forename: Mark
authors.initials: M
authors.lastname: Coburn
authors.affiliation: Department of Thoracic &amp; Cardiovascular Surgery, University Hospital RWTH, 52074 Aachen, Germany. agoetzenich@ukaachen.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Goetzenich
authors.affiliation: Department of Anesthesiology, University Hospital RWTH, 52074 Aachen, Germany. christian.stoppe@gmail.com.|Department of Intensive Care Medicine, University Hospital RWTH, 52074 Aachen, Germany. christian.stoppe@gmail.com.
authors.forename: Christian
authors.initials: C
authors.lastname: Stoppe
mesh_terms: D000818:Animals; D001128:Argon / Q000494:pharmacology*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D006331:Heart Diseases / Q000517:prevention & control*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D019157:Ischemic Preconditioning, Myocardial; D032383:Myocytes, Cardiac / Q000187:drug effects*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D001128:Argon; D006360:Heat-Shock Proteins; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase; D042461:Vascular Endothelial Growth Factor A; D000099156:Superoxide Dismutase 2
keywords: argon; cardiomyocytes; cardioprotection; late phase of preconditioning