N-3 PUFAs protect against aortic inflammation and oxidative stress in angiotensin II-infused apolipoprotein E-/- mice

PLoS One. 2014 Nov 14;9(11):e112816. doi: 10.1371/journal.pone.0112816. eCollection 2014.

Abstract

Abdominal aortic aneurysm is associated with infiltration of inflammatory cells into the aortic wall. The inflammatory response is also evident in animal models, such as apolipoprotein E-deficient (ApoE-/-) mice that have been infused with angiotensin II, prior to development of aortic aneurysm. Since omega-3 polyunsaturated fatty acids (n-3 PUFAs) and their metabolites have anti-inflammatory and pro-resolving activity, we hypothesised that dietary supplementation with n-3 PUFAs would protect against inflammatory processes in this mouse model. Twenty C57 and 20 ApoE-/- 3-4 week old male mice were supplemented with a low (0.14%, n = 10/group) or high (0.70%, n = 10/group) n-3 PUFA diet for 8 weeks before 2-day infusion with 0.9% saline or angiotensin II (1000 ng/kg/min). Four ApoE-/- mice on the low n-3 PUFA diet and none of the ApoE-/- mice on the high n-3 PUFA diet showed morphological evidence of abdominal aortic dissection. The plasma concentration of the n-3 PUFA metabolite, resolvin D1 was higher in angiotensin II-infused ApoE-/- mice fed the high, compared to the low n-3 PUFA diet. The number of neutrophils and macrophages infiltrating the abdominal aorta was elevated in ApoE-/- mice on the low n-3 PUFA diet, and this was significantly attenuated in mice that were fed the high n-3 PUFA diet. Most neutrophils and macrophages were associated with dissected aortas. Immunoreactivity of the catalytic subunit of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, Nox2, and superoxide were elevated in ApoE-/- mice that were fed the low n-3 PUFA diet, and this was also significantly attenuated in mice that were fed the high n-3 PUFA diet. Together, the findings indicate that supplementation of ApoE-/- mice with a diet high in n-3 PUFA content protected the mice against pro-inflammatory and oxidative stress responses following short-term infusion with angiotensin II.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / pharmacology*
  • Animals
  • Aorta / metabolism*
  • Aorta / pathology
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism*
  • Body Weight / drug effects
  • Cholesterol / blood
  • Dietary Supplements
  • Docosahexaenoic Acids / blood
  • Fatty Acids, Omega-3 / pharmacology*
  • Inflammation
  • Macrophages / cytology
  • Macrophages / immunology
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Animal
  • NADPH Oxidase 2
  • NADPH Oxidases / metabolism
  • Neutrophils / cytology
  • Neutrophils / immunology
  • Oxidative Stress / drug effects*
  • Superoxides / metabolism
  • Triglycerides / blood

Substances

  • Apolipoproteins E
  • Fatty Acids, Omega-3
  • Membrane Glycoproteins
  • Triglycerides
  • resolvin D1
  • Superoxides
  • Angiotensin II
  • Docosahexaenoic Acids
  • Cholesterol
  • Cybb protein, mouse
  • NADPH Oxidase 2
  • NADPH Oxidases

Grants and funding

This study was funded by a Faculty Seed Grant to FR. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.