title: Aging dysregulates D- and E-series resolvins to modulate cardiosplenic and cardiorenal network following myocardial infarction.
abstract: Post-myocardial infarction (MI), overactive inflammation is the hallmark of aging, however, the mechanism is unclear. We hypothesized that excess influx of omega 6 fatty acids may impair resolution, thus impacting the cardiosplenic and cardiorenal network post-MI. Young and aging mice were fed on standard lab chow (LC) and excess fatty acid (safflower oil; SO)-enriched diet for 2 months and were then subjected to MI surgery. Despite similar infarct areas and left ventricle (LV) dysfunction post-MI, splenic mass spectrometry data revealed higher levels of arachidonic acid (AA) derived pro-inflammatory metabolites in young-SO, but minimal formation of docosanoids, D- and E- series resolvins in SO-fed aged mice. The aged mice receiving excess intake of fatty acids exhibit; 1) decreased lipoxygenases (5-,12-, and 15) in the infarcted LV; 2) lower levels of 14HDHA, RvD1, RvD5, protectin D1, 7(S)maresin1, 8-,11-,18-HEPE and RvE3 with high levels of tetranor-12-HETEs; 3) dual population of macrophages (CD11blow/F480highand CD11bhigh/F480high) with increased pro-inflammatory (CD11bp+F4/80+Ly6Chi) phenotype and; 4) increased kidney injury marker NGAL with increased expression of TNF-α and IL-1β indicating MI-induced non-resolving response compared with LC-group. Thus, excess fatty acid intake magnifies the post-MI chemokine signaling and inflames the cardiosplenic and cardiorenal network towards a non-resolving microenvironment in aging.
authors: Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, AL 35233, USA.
authors: Ganesh V
authors: GV
authors: Halade
authors: Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, AL 35233, USA.
authors: Vasundhara
authors: V
authors: Kain
authors: Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, AL 35233, USA.
authors: Laurence M
authors: LM
authors: Black
authors: Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, AL 35233, USA.
authors: Sumanth D
authors: SD
authors: Prabhu
authors: Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, AL 35233, USA.
authors: Kevin A
authors: KA
authors: Ingle
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D015118:Eicosapentaenoic Acid / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D000071068:Lipocalin-2 / Q000378:metabolism; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D000071068:Lipocalin-2; D014409:Tumor Necrosis Factor-alpha; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid
keywords: aging; lipid mediators; lipoxygenase; macrophages; myocardial infarction; non-resolving inflammation