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Article
Aging Dysregulates D- and E-Series Resolvins to Modulate Cardiosplenic and Cardiorenal Network Following Myocardial Infarction
Aging
  • Ganesh V. Halade, The University of Alabama at Birmingham
  • Vasundhara Kain, The University of Alabama at Birmingham
  • Laurence M. Black, The University of Alabama at Birmingham
  • Sumanth D. Prabhu, The University of Alabama at Birmingham
  • Kevin A. Ingle, The University of Alabama at Birmingham
Document Type
Article
Publication Date
1-1-2016
Keywords
  • Aging,
  • Lipid mediators,
  • Lipoxygenase,
  • Macrophages,
  • Myocardial infarction,
  • Non-resolving inflammation
Digital Object Identifier (DOI)
https://doi.org/10.18632/aging.101077
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/F480high and CD11bhigh/F480high) with increased pro-inflammatory (CD11b+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.

Rights Information
Creative Commons Attribution 3.0
Citation / Publisher Attribution

Aging, v. 8, issue 11, p. 2611-2634

Citation Information
Ganesh V. Halade, Vasundhara Kain, Laurence M. Black, Sumanth D. Prabhu, et al.. "Aging Dysregulates D- and E-Series Resolvins to Modulate Cardiosplenic and Cardiorenal Network Following Myocardial Infarction" Aging Vol. 8 Iss. 11 (2016) p. 2611 - 2634
Available at: http://works.bepress.com/ganesh-halade/13/