High phosphate diet reduces atherosclerosis formation in apolipoprotein E-deficient mice

  • Shiota Asuka
    Department of Clinical Nutrition, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Taketani Yutaka
    Department of Clinical Nutrition, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Maekawa Yoichi
    Department of Immunology and Parasitology, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Yasutomo Koji
    Department of Immunology and Parasitology, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Sata Masataka
    Department of Cardiovascular Medicine, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Sakai Tohru
    Department of Public Health and Applied Nutrition, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Mizuno Risuke
    Department of Molecular Vascular Endocrinology, Graduate School of Medicine, University of Tokyo
  • Isshiki Masashi
    Department of Molecular Vascular Endocrinology, Graduate School of Medicine, University of Tokyo
  • Yamamoto Hironori
    Department of Clinical Nutrition, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Takeda Eiji
    Department of Clinical Nutrition, Institute of Health Biosciences, the University of Tokushima Graduate School

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Abstract

Although higher serum phosphate level is a risk factor for cardiovascular diseases in general population as well as chronic kidney disease patients, it has not been clarified whether higher phosphate can affect atherosclerotic plaque formation. In this study, we investigated the effect of prolonged-intake of different concentrations of phosphate on atherosclerosis formation using apolipoprotein E-deficient mice. Apolipoprotein E-deficient mice were fed with high fat diet including 0.6%, 1.2% or 1.8% phosphate. After 20-week treatment, atherosclerotic plaque formation in aorta in 1.8% phosphate diet group was unexpectedly less than that in the other groups. To elucidate mechanisms of suppression of plaque formation by high phosphate diet, we hypothesized that high phosphate diet may modify a profile of monocytes/macrophages suppressing plaque formation. We confirmed that elevated peripheral monocytes (CD11b+, F4/80+ cell numbers) in apolipoprotein E-deficient mice were decreased by feeding with 1.8% P diet. In addition, ex vivo study indicated that high dose of phosphate induced macrophage apoptosis. These observations suggest that excess phosphate intake decreased atherosclerosis formation, at least in part, by changing the profile of peripheral monocytes or inducing apoptosis of macrophages in apolipoprotein E-deficient mice.<br>

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