期刊
AGING-US
卷 8, 期 11, 页码 2611-2634出版社
IMPACT JOURNALS LLC
DOI: 10.18632/aging.101077
关键词
aging; non-resolving inflammation; lipid mediators; lipoxygenase; macrophages; myocardial infarction
资金
- NIH-NCCIH [AT006704, HL132989-01]
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)maresinl, 8-,11-,18-HEPE and RvE3 with high levels of tetranor-12-HETEs; 3) dual population of macrophages (CD11b(low)/F480(high) and CD11b(high)/F480(high)) with increased pro-inflammatory (CD11b(+)F4/80(+)Ly6C(hi)) phenotype and; 4) increased kidney injury marker NGAL with increased expression of TNF-alpha and 11-1 beta 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.
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