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

Am J Physiol Heart Circ Physiol. 2015 Feb 15;308(4):H269-80. doi: 10.1152/ajpheart.00604.2014. Epub 2014 Dec 5.


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-1γ 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-lipoxygenase, 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.

Keywords: inflammation; lipid mediators; lipidomics; neutrophils; polyunsaturated fatty acids; proteomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / metabolism
  • Aging / metabolism*
  • Animals
  • Arachidonic Acid / metabolism
  • CD40 Antigens / metabolism
  • Cyclooxygenase 2 / metabolism
  • Diet, High-Fat / adverse effects
  • Fatty Acids, Omega-3 / metabolism
  • Heme Oxygenase-1 / metabolism
  • Inflammation / metabolism
  • Lipoxygenase / metabolism
  • Macrophage Inflammatory Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Infarction / complications
  • Myocardial Infarction / immunology
  • Myocardial Infarction / metabolism*
  • Myocardial Infarction / physiopathology
  • Neutrophil Infiltration
  • Obesity / etiology
  • Obesity / metabolism*
  • Obesity / physiopathology
  • Ventricular Function
  • Wound Healing


  • CD40 Antigens
  • Fatty Acids, Omega-3
  • Macrophage Inflammatory Proteins
  • Arachidonic Acid
  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
  • Lipoxygenase
  • Heme Oxygenase-1
  • Cyclooxygenase 2