Research Paper Volume 8, Issue 11 pp 2611—2634

Aging dysregulates D- and E-series resolvins to modulate cardiosplenic and cardiorenal network following myocardial infarction

Ganesh V. Halade1, , Vasundhara Kain1, , Laurence M. Black1, , Sumanth D. Prabhu1, , Kevin A. Ingle1, ,

  • 1 Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, AL 35233, USA

Received: July 20, 2016       Accepted: October 1, 2016       Published: October 18, 2016
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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 (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.


AA: Arachidonic acid; CD: Cluster of differentiation; COX: Cyclooxygenase; DHA: Docosahexaenoic acid; DPA: Docosapentaenoic acid; EETs: Epoxyeicosatrienoic acids; EPA: Eicosapentaenoic acid; HDHA: Hydroxydocosahexaenoic acid; HEPE: Hydroxyeico-sapentaenoic acid; HETEs: Hydroperoxyeicosatetraenoic acid; HODEs: Hydroxyoctadecadienoic acids; HF: Heart Failure; IL-6: Interleukin 6; IL-1β: Interleukin-1beta; LC: Lab chow; LC-MS/MS: Liquid chromatography mass spectrometry; LOX: lipoxygenase; LT: Leukotrienes; LV: Left ventricle; MI: Myocardial infarction; NGAL: Neutrophil gelatinase-associated lipocalin; PGs: Prostaglandins; Rv: Resolvin; SO: Safflower oil; TNF-α: tumor necrosis factor alpha; TX: Thromboxane.