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Non‐Resolving Chemokine Response Dysregulates Cardiosplenic And Cardiorenal Network Following Myocardial Infarction In Aging
Author(s) -
Halade Ganesh V,
Kain Vasundhara,
Ingle Kevin,
Black Laurence M
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1208.1
Subject(s) - medicine , endocrinology , chemokine , inflammation , myocardial infarction , kidney , immunology
Chemokine signal drives the innate inflammatory response following myocardial infarction (MI), though how it provokes non‐resolving chronic inflammation in aging is unclear. To answer this, we hypothesized that resolution reprograms, specifically proresolving lipid mediators formed in innate immune response, may be dysregulated in aging post‐MI, influencing cardiorenal and cardiosplenic network. Young (6 months) and aging (18 months) mice were fed standard lab chow (LC) and safflower oil (SO)‐enriched diet for 2 months and were then subjected to coronary artery ligation in order to induce MI. Despite similar infarct areas and reduced fractional shortening post‐MI, splenic mass spectroscopy lipid profiling revealed higher levels arachidonic acid (AA) derived pro‐inflammatory metabolites, but minimal formation of eicosanoids, docosanoids D‐ and E‐ series resolvins in SO‐fed group compared with LC group. SO fed aging mice displayed higher levels of pro‐inflammatory thromboxanes and tetranor‐12‐HETEs metabolites (p<.0.5) compared to adult‐SO fed mice. Data suggests that aging decreases the expression levels of 12‐lipoxyegenase (LOX) and 15‐LOX and 5‐LOX (all p<0.05) in infarcted left ventricle compared to young LC fed mice, but increased in kidney and spleen post‐MI. Excess intake of SO decreased formyl peptide receptor 2 ( FPR2 ) compared to young SO‐fed mice, indicating non‐resolving response Increased SO intake also caused higher NGAL expression, suggesting kidney injury with LC group. The decreased expression of Arg‐1 in response to MI suggested the delayed healing in aging mice compared to young mice. In summary, aging magnifies the post‐MI chemokine‐driven innate response and impairs the healing response by stimulating prolonged neutrophil trafficking and proinflammatory lipid mediators. Support or Funding Information The authors acknowledge support from NIH‐NCCAM K99/R00 AT006704 and UAB start‐up funds, awarded to GVH.