Obesity superimposed on aging magnifies inflammation and delays the resolving response after myocardial infarction

Elizabeth F. Lopez, Janusz H. Kabarowski, Kevin A. Ingle, Vasundhara Kain, Stephen Barnes, David K. Crossman, Merry L. Lindsey, Ganesh V. Halade

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Polyunsaturated fatty acid (PUFA) intake has increased over the last 100 yr, contributing to the current obesogenic environment. Obesity and aging are prominent risk factors for myocardial infarction (MI). How obesity interacts with aging to alter the post-MI response, however, is unclear. We tested the hypothesis that obesity in aging mice would impair the resolution of post-MI inflammation. PUFA diet (PUFA aging group) feeding to 12-mo-old C57BL/6J mice for 5 mo showed higher fat mass compared with standard lab chow (LC)-fed young (LC young group; 3-5 mo old) or aging alone control mice (LC aging group). LC young, LC aging, and PUFA aging mice were subjected to coronary artery ligation to induce MI. Despite similar infarct areas post-MI, plasma proteomic profiling revealed higher VCAM-1 in the PUFA aging group compared with LC young and LC aging groups, leading to increased neutrophil infiltration in the PUFA aging group (P < 0.05). Macrophage inflammatory protein-17 and CD40 were also increased at day 1, and myeloperoxidase remained elevated at day 5, an observation consistent with delayed wound healing in the PUFA aging group. Lipidomic analysis showed higher levels of arachidonic acid and 12(S)-hydroxyeicosatetraenoic acid at day 1 post-MI in the PUFA aging group compared with the LC aging group (all P < 0.05), thereby mediating neutrophil extravasation in the PUFA aging group. The inflammation-resolving enzymes 5-li-poxygenase, cyclooxygenase-2, and heme oxyegnase-1 were altered to delay wound healing post-MI in the PUFA aging group compared with LC young and LC aging groups. PUFA aging magnifies the post-MI inflammatory response and impairs the healing response by stimulating prolonged neutrophil trafficking and proinflammatory lipid mediators.

Original languageEnglish (US)
Pages (from-to)H269-H280
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume308
Issue number4
DOIs
StatePublished - 2015

Keywords

  • Inflammation
  • Lipid mediators
  • Lipidomics
  • Neutrophils
  • Polyunsaturated fatty acids
  • Proteomics

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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