title: Obesity superimposed on aging magnifies inflammation and delays the resolving response after myocardial infarction.
abstract: Polyunsaturated fatty acid (PUFA) intake has increased over the last 100 yr, contributing to the current obesogenic environment. Obesity and aging are prominent risk factors for myocardial infarction (MI). How obesity interacts with aging to alter the post-MI response, however, is unclear. We tested the hypothesis that obesity in aging mice would impair the resolution of post-MI inflammation. PUFA diet (PUFA aging group) feeding to 12-mo-old C57BL/6J mice for 5 mo showed higher fat mass compared with standard lab chow (LC)-fed young (LC young group; 3-5 mo old) or aging alone control mice (LC aging group). LC young, LC aging, and PUFA aging mice were subjected to coronary artery ligation to induce MI. Despite similar infarct areas post-MI, plasma proteomic profiling revealed higher VCAM-1 in the PUFA aging group compared with LC young and LC aging groups, leading to increased neutrophil infiltration in the PUFA aging group (P<0.05). Macrophage inflammatory protein-1γ and CD40 were also increased at day 1, and myeloperoxidase remained elevated at day 5, an observation consistent with delayed wound healing in the PUFA aging group. Lipidomic analysis showed higher levels of arachidonic acid and 12(S)-hydroxyeicosatetraenoic acid at day 1 post-MI in the PUFA aging group compared with the LC aging group (all P<0.05), thereby mediating neutrophil extravasation in the PUFA aging group. The inflammation-resolving enzymes 5-lipoxygenase, cyclooxygenase-2, and heme oxyegnase-1 were altered to delay wound healing post-MI in the PUFA aging group compared with LC young and LC aging groups. PUFA aging magnifies the post-MI inflammatory response and impairs the healing response by stimulating prolonged neutrophil trafficking and proinflammatory lipid mediators.
authors.affiliation: The University of Texas Medical Branch, Galveston, Texas;
authors.forename: Elizabeth F
authors.initials: EF
authors.lastname: Lopez
authors.affiliation: Department of Microbiology, The University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Janusz H
authors.initials: JH
authors.lastname: Kabarowski
authors.affiliation: Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Ingle
authors.affiliation: Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Vasundhara
authors.initials: V
authors.lastname: Kain
authors.affiliation: Targeted Metabolomics and Proteomics Laboratory, The University of Alabama at Birmingham, Birmingham, Alabama; Department of Pharmacology and Toxicology, The University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Stephen
authors.initials: S
authors.lastname: Barnes
authors.affiliation: Department of Genetics, The University of Alabama at Birmingham, Birmingham, Alabama; and.
authors.forename: David K
authors.initials: DK
authors.lastname: Crossman
authors.affiliation: Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, and Research Service, G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, Mississippi.
authors.forename: Merry L
authors.initials: ML
authors.lastname: Lindsey
authors.affiliation: Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama; halade@uab.edu.
authors.forename: Ganesh V
authors.initials: GV
authors.lastname: Halade
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D015525:Fatty Acids, Omega-3 / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000150:complications / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D020556:Neutrophil Infiltration; D009765:Obesity / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D016276:Ventricular Function; D014945:Wound Healing
chemical_list: D019013:CD40 Antigens; D015525:Fatty Acids, Omega-3; D019402:Macrophage Inflammatory Proteins; D016718:Arachidonic Acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D008084:Lipoxygenase; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2
keywords: inflammation; lipid mediators; lipidomics; neutrophils; polyunsaturated fatty acids; proteomics