title: High-density lipoproteins reduce palmitate-induced cardiomyocyte apoptosis in an AMPK-dependent manner.
abstract: Palmitate has been implicated in the induction of cardiomyocyte apoptosis via reducing the activity of 5' AMP-activated protein kinase (AMPK). We sought to evaluate whether high-density lipoproteins (HDLs), known for their cardioprotective features and their potential to increase AMPK activity, can reduce palmitate-induced cardiomyocyte apoptosis and whether this effect is AMPK-dependent. Therefore, cardiomyocytes were isolated from adult Wistar rat hearts via perfusion on a Langendorff-apparatus and cultured in free fatty acid-free BSA control medium or 0.5 mM palmitate medium in the presence or absence of HDL (5 μg protein/ml) with or without 0.1 μM of the AMPK-inhibitor compound S for the analysis of Annexin V/propidium, genes involved in apoptosis and fatty acid oxidation, and cardiomyocyte contractility. We found that HDLs decreased palmitate-induced cardiomyocyte apoptosis as indicated by a reduction in Annexin V-positive cardiomyocytes and an increase in Bcl-2 versus Bax ratio. Concomitantly, HDLs increased the palmitate-impaired expression of genes involved in fatty acid oxidation. Furthermore, HDLs improved the palmitate-impaired cardiomyocyte contractility. All effects were mediated in an AMPK-dependent manner, concluding that HDLs reduce palmitate-induced cardiomyocyte apoptosis, resulting in improved cardiomyocyte contractility through a mechanism involving AMPK.
authors.affiliation: Charité-University-Medicine Berlin, Campus Virchow Klinikum, Department of Cardiology, Berlin, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Spillmann
authors.affiliation: Department of Internal Medicine I, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Trimpert
authors.affiliation: Charité-University-Medicine Berlin, Campus Virchow Klinikum, Department of Cardiology, Berlin, Germany.
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Internal Medicine I, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Lars G
authors.initials: LG
authors.lastname: Eckerle
authors.affiliation: Department of Internal Medicine I, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Staudt
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies, Charité, University Medicine Berlin, Campus Virchow, Berlin, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Warstat
authors.affiliation: Department of Internal Medicine I, University Medicine Greifswald, Greifswald, Germany; Deutsches Zentrum für Herz Kreislaufforschung (DZHK), Standort Greifswald, Germany.
authors.forename: Stephan B
authors.initials: SB
authors.lastname: Felix
authors.affiliation: Charité-University-Medicine Berlin, Campus Virchow Klinikum, Department of Cardiology, Berlin, Germany; Deutsches Zentrum für Herz Kreislaufforschung (DZHK), Standort Berlin/Charité, Germany.
authors.forename: Burkert
authors.initials: B
authors.lastname: Pieske
authors.affiliation: Charité-University-Medicine Berlin, Campus Virchow Klinikum, Department of Cardiology, Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies, Charité, University Medicine Berlin, Campus Virchow, Berlin, Germany; Deutsches Zentrum für Herz Kreislaufforschung (DZHK), Standort Berlin/Charité, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Tschöpe
authors.affiliation: Charité-University-Medicine Berlin, Campus Virchow Klinikum, Department of Cardiology, Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies, Charité, University Medicine Berlin, Campus Virchow, Berlin, Germany; Deutsches Zentrum für Herz Kreislaufforschung (DZHK), Standort Berlin/Charité, Germany. Electronic address: sophie.van-linthout@charite.de.
authors.forename: Sophie
authors.initials: S
authors.lastname: Van Linthout
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D005260:Female; D008075:Lipoproteins, HDL / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects*; D019308:Palmitic Acid / Q000494:pharmacology*; D051381:Rats
chemical_list: D008075:Lipoproteins, HDL; D019308:Palmitic Acid; D000263:Adenylate Kinase
keywords: Cardiomyocyte; HDL; Lipoptoxicity; Palmitate