title: Acrolein consumption exacerbates myocardial ischemic injury and blocks nitric oxide-induced PKCepsilon signaling and cardioprotection.
abstract: Aldehydes are common reactive constituents of food, water and air. Several food aldehydes are potentially carcinogenic and toxic; however, the direct effects of dietary aldehydes on cardiac ischemia-reperfusion (IR) injury are unknown. We tested the hypothesis that dietary consumption of aldehydes modulates myocardial IR injury and preconditioning. Mice were gavage-fed the alpha, beta-unsaturated aldehyde acrolein (5mg/kg) or water (vehicle) 24h prior to a 30-min coronary artery occlusion and 24-hour reperfusion. Myocardial infarct size was significantly increased in acrolein-treated mice, demonstrating that acute acrolein exposure worsens cardiac IR injury. Furthermore, late cardioprotection afforded by the nitric oxide (NO) donor diethylenetriamine/NO (DETA/NO; dose: 0.1mg/kg x 4, i.v.) was abrogated by the administration of acrolein 2h prior to DETA/NO treatment, indicating that oral acrolein impairs NO donor-induced late preconditioning. To examine potential intracellular targets of aldehydes, we investigated the impact of acrolein on mitochondrial PKCepsilon signaling in the heart. Acrolein-protein adducts were formed in a dose-dependent manner in isolated cardiac mitochondria in vitro and specific acrolein-PKCepsilon adducts were present in cardiac mitochondrial fractions following acrolein exposure in vivo, demonstrating that mitochondria are major targets of aldehyde toxicity. Furthermore, DETA/NO preconditioning induced both PKCepsilon translocation and increased mitochondrial PKCepsilon localization. Both of these responses were blocked by acrolein pretreatment, providing evidence that aldehydes disrupt cardioprotective signaling events involving PKCepsilon. Consumption of an aldehyde-rich diet could exacerbate cardiac IR injury and block NO donor-induced cardioprotection via mechanisms that disrupt PKCepsilon signaling.
authors.affiliation: Department of Physiology and the Cardiovascular Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Institute of Molecular Cardiology, Department of Medicine/Cardiology, University of Louisville, Louisville, KY, USA.
authors.forename: Guang-Wu
authors.initials: GW
authors.lastname: Wang
authors.affiliation: Institute of Molecular Cardiology, Department of Medicine/Cardiology, University of Louisville, Louisville, KY, USA.
authors.forename: Yiru
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Physiology and the Cardiovascular Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Vondriska
authors.affiliation: Department of Physiology and the Cardiovascular Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Molecular Cardiology, Department of Medicine/Cardiology, University of Louisville, Louisville, KY, USA.
authors.forename: Su
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Physiology and the Cardiovascular Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Linda L
authors.initials: LL
authors.lastname: Tsai
authors.affiliation: Department of Physiology and the Cardiovascular Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Nobel C
authors.initials: NC
authors.lastname: Zong
authors.affiliation: Institute of Molecular Cardiology, Department of Medicine/Cardiology, University of Louisville, Louisville, KY, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bolli
authors.affiliation: Institute of Molecular Cardiology, Department of Medicine/Cardiology, University of Louisville, Louisville, KY, USA.
authors.forename: Aruni
authors.initials: A
authors.lastname: Bhatnagar
authors.affiliation: Institute of Molecular Cardiology, Department of Medicine/Cardiology, University of Louisville, Louisville, KY, USA; Medical Service, Louisville VA Medical Center, Louisville, KY, USA. Electronic address: sprabhu@louisville.edu.
authors.forename: Sumanth D
authors.initials: SD
authors.lastname: Prabhu
mesh_terms: D000171:Acrolein / Q000633:toxicity*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D004032:Diet / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008813:Mice, Inbred ICR; D008929:Mitochondria, Heart / Q000201:enzymology* / Q000473:pathology; D009203:Myocardial Infarction / Q000201:enzymology* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000473:pathology; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D014226:Triazenes / Q000494:pharmacology
chemical_list: C105351:1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene; D002316:Cardiotonic Agents; D014226:Triazenes; D000171:Acrolein; D051744:Protein Kinase C-epsilon