Abstract 13792: Inhibitory Effects of Eicosapentaenoic Acid on Arterial Calcification in Klotho Mutant Mice
Background: The klotho gene was identified as an “aging-suppressor” gene in mice that accelerates arterial calcification when disrupted. Expression levels of serum and local vascular klotho are reduced in patients with chronic kidney disease (CKD) and that the decrease in expression level of klotho is associated with arterial calcification. Intake of eicosapentaenoic acid (EPA), an n-3 fatty acid, reduces the risk of fatal coronary artery disease. However, the effects of EPA on arterial calcification have not been fully elucidated.
Purpose: The aim of this study was to evaluate the effect of EPA on arterial calcification in klotho mutant mice.
Methods: Four-week-old klotho mutant mice (n=24, 12 males & 12 females) and wild-type (WT) mice (n=24, 12 males & 12 females) were given a diet containing 5% EPA (EPA food, klotho and WT: n=12, each) or not containing EPA (control food, klotho and WT: n=12, each) for 4 weeks. Calcium volume score (CVS) of the thoracic and abdominal aorta was assessed by multi-detector computed tomography.
Results: CVS were significantly elevated in klotho mice after 4 weeks of control food (before vs after feeding, P<0.05), but they were not elevated in klotho mice after 4 weeks of EPA food and in WT mice after 4 weeks of control or EPA food (before vs after feeding, P=NS). Change in CVS in control food-fed klotho mice (Δ calcium volume score: 81±28 mm3) was significantly greater than that in EPA-fed klotho mice (18±17 mm3, P<0.05) and that in control food-fed WT mice (8±6 mm3, P<0.005) or EPA-fed WT mice (2±11 mm3, P<0.005). Activity of NADPH oxidase (NOX), an enzyme that generates superoxide, and expression level of NOX4 gene were significantly higher in arterial smooth muscle cells (SMCs) of klotho mutant mice than in those of WT mice. mRNA of the gene encoding G-protein-coupled receptor 120 (GPR120), a receptor of n-3 fatty acids, was expressed in arterial SMCs. EPA decreased expression levels of the NOX4 gene and NOX activity. GPR120 gene knockdown by siRNA canceled out the effects of EPA on NOX4 gene expression and NOX activity in arterial SMCs of klotho mutant mice.
Conclusions: Administration of EPA prevents arterial calcification together with reduction of expression levels of the NOX4 gene and NOX activity via GPR120 in klotho mutant mice.
Author Disclosures: K. Nakamura: None. D. Miura: None. K. Yunoki: None. Y. Koyama: None. Y. Saito: None. M. Satoh: None. K. Osawa: None. T. Miyoshi: None. K. Kohno: None. H. Morita: None. H. Ito: None.
- © 2014 by American Heart Association, Inc.