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

Figures

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  Figure 1. Excess fatty acid influx depleted LOXs in young and aging post-MI (A) Study design indicating young (6 months) and aging (18 months) mice on an omega-6 fatty acids enriched safflower oil diet protocol. (B) No-MI naïve control and infarcted LV stained with periodic acid-Schiff (PAS) at d1 post-MI in young and aging, with and without fatty acid enriched diet. No-MI control represents the steady state naïve control mice (C) mRNA expression of LOXs (5,12,15) and TNF-ɑ in infarcted LV. *p<0.05 vs young-LC; $ p<0.05 LC vs SO. Values are means ±SEM; n=2-4/group.

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  Figure 2. Aging and intake of fatty acids impacts metabololipidomics profiling in LV healing (A and B) Hierarchal cluster analyses of lipids indicates increased levels of metabolites in young but decreased in SO diet fed aging group post-MI. Color code bar representing change in expression from green (-1 lowest decrease) to red (+1 highest increase). (C) Venn diagram representing the number of metabolites affected due to age (young vs aging) and SO diet post-MI. (D) Principal component analysis (PCA) of lipid metabolites suggesting limited intake of fatty acids in young and aging (LC) mice respond similar manner post-MI; n =3/group.

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  Figure 3. Excess fatty acids in aging decreases arachidonic acid (AA) metabololipidome post-MI (A) Hierarchal cluster analysis of change in AA metabolites due to young and aging with and without SO diet. Color code bar representing change in expression from green (-1 lowest decrease) to red (+1 highest increase). (B) Venn diagram representing the number of AA metabolites affected due to age (young and aging) and SO-diet post-MI. (C) PCA analysis of AA metabolites of post-MI with respect to age and diet. (D) Bar graph representing change in AA metabolite production at pre-MI (No-MI controls) and d1 post-MI.

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  Figure 4. Excess omega-6 fatty acids dysregulate DHA metabololipidomics profile post-MI (A) Hierarchal cluster analysis of change in DHA metabolites in young and aging, with and without SO diet. Color code bar representing change in expression from green (-1 lowest decrease) to red (+1 highest increase). (B) Venn diagram representing the number of DHA metabolites affected due to age (young and aging) and SO diet post-MI. (C) PCA analysis of DHA metabolites with respect to age and diet post-MI. (D) Bar graph representing change in DHA metabolite production at pre-MI (No-MI controls) and d1 post-MI.

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  Figure 5. Excess intake of omega-6 fatty acids increased F4/80+/Ly6Chigh Ly6G+, CD11b+ population post-MI (A) Representative dot plots identifying CD11b+ population in LV mononuclear cells isolated from LC and SO fed young mice at d1 post-MI. (B) Representative flow cytometry (FACs) dot plots showing Ly6Chigh in LV mononuclear cells isolated from LC and SO fed young and aging mice at d1 post-MI. (C) Bar graphs representing percentage of Ly6G+ population in LV mononuclear cells at d1 post-MI. (D) Bar graphs representing percentage of Ly6Chigh population in LV mononuclear cells at d1 post-MI. (E) Representative FACs dot plots showing CD45+/CD11b+ in LV mononuclear cells isolated from LC and SO fed young and aging mice at d1 post-MI. (F) Representative FACs dot plots showing CD11blow/F4/80high and CD11bhigh/F4/80high in LV mononuclear cells isolated from LC and SO fed young and aging mice at d1 post-MI. (G) Bar graphs representing percentage of CD11b+ population in LV mononuclear cells at d1 post-MI. (H) Histogram representing change in CD11b expression in young and aging mice post-MI. *p<0.05 vs young-LC; $ p<0.05 LC vs SO. n=3-5 mice/group for flow cytometry analysis.

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  Figure 6. Post-MI impact of fatty acids during aging on cardiorenal-axis (A) Immunofluorescence images representing TUNEL positive cells (green) in young and aging-SO fed mice. Nuclei are stained with propidium iodide (Red). (B) PAS staining indicates granulomatous kidney inflammation. (C) Pre- and post-MI plasma creatinine level and mRNA expression of TNF-α and IL-1β, in kidney. (D) Pre- and post-MI mRNA and protein expression of NGAL in kidney. *p<0.05 vs young-LC; $p<0.05 LC vs SO. Values are means ±SEM; n=; n=2 at d0, n=3-4 at d1/group.

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  Figure 7. Schematic summary indicating the dysregulation of MI-induced cardiorenal and cardiosplenic network in aging.