Suboptimal dietary zinc intake promotes vascular inflammation and atherogenesis in a mouse model of atherosclerosis

Mol Nutr Food Res. 2012 Jul;56(7):1097-105. doi: 10.1002/mnfr.201100776.

Abstract

Scope: Cardiovascular health is strongly influenced by diet. Zinc has antioxidant and anti-inflammatory properties but its long-term influence on vascular health at dietary intake levels relevant to the human population in developed countries has not been studied. We investigated the influence of suboptimal zinc intake in a Western-type diet on the development of vascular inflammation and arterial plaque in apoE knock-out (AEKO) mice.

Methods and results: Weanling AEKO and wild-type (WT) controls were given high saturated fat (21% w/w) and high cholesterol (0.15%) semi-synthetic diets containing 3 or 35 mg Zn/kg (AEKO and WT) or 8 mg Zn/kg (AEKO only) for over 6 months. AEKO mice on zinc intakes of 3 and 8 mg Zn/kg (suboptimal zinc) developed significantly (p < 0.05) more aortic plaque than AEKO mice consuming 35 mg Zn/kg (adequate zinc). Circulating levels of interleukin-1β, interleukin-6 and soluble vascular adhesion molecule-1 were significantly (p < 0.05) raised at the lowest zinc intake in AEKO mice, as compared to zinc-adequate controls. Plasma total cholesterol and total protein were also significantly (p < 0.05) increased at the lowest zinc intake.

Conclusion: We propose that suboptimal dietary zinc intake raises circulating pro-atherogenic lipoprotein levels that promote vascular inflammation and enhance arterial plaque formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antioxidants / administration & dosage
  • Antioxidants / therapeutic use
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism
  • Atherosclerosis / blood
  • Atherosclerosis / etiology*
  • Atherosclerosis / immunology
  • Atherosclerosis / prevention & control
  • Calcinosis / etiology
  • Calcinosis / immunology
  • Calcinosis / pathology
  • Calcinosis / prevention & control
  • Diet / adverse effects*
  • Diet, Atherogenic / adverse effects
  • Disease Models, Animal*
  • Interleukins / blood
  • Mice
  • Mice, Congenic
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Plaque, Atherosclerotic / etiology
  • Plaque, Atherosclerotic / immunology
  • Plaque, Atherosclerotic / pathology
  • Plaque, Atherosclerotic / prevention & control
  • Random Allocation
  • Severity of Illness Index
  • Vascular Cell Adhesion Molecule-1 / blood
  • Vasculitis / blood
  • Vasculitis / etiology*
  • Vasculitis / immunology
  • Vasculitis / prevention & control
  • Zinc / administration & dosage
  • Zinc / deficiency*
  • Zinc / therapeutic use

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Apolipoproteins E
  • Interleukins
  • Vascular Cell Adhesion Molecule-1
  • Zinc