Klotho protein protects against endothelial dysfunction

Yuichiro Saito, Takahiro Yamagishi, Tetsuya Nakamura, Yoshio Ohyama, Hiroki Aizawa, Tatsuo Suga, Yutaka Matsumura, Hiroaki Masuda, Masahiko Kurabayashi, Makoto Kuro-O, Yo Ichi Nabeshima, Ryozo Nagai

Research output: Contribution to journalArticlepeer-review

210 Scopus citations

Abstract

Arteriosclerosis caused by aging is recognized to be a crucial risk factor of cardiovascular disease. We recently established klotho mouse which causes age-related disorders including arteriosclerosis. However, no information on endothelial function of klotho mouse or the physiological role of klotho protein as a circulating factor is available. In this report, we demonstrate that 50% effective dose of aortic relaxation in response to acetylcholine in heterozygous klotho mice is significantly greater (4 x 10-5 M) than in wild-type mice (8 x 10-6 M, n = 7, p < 0.05) and that the vasodilator response of arterioles to acetylcholine is significantly attenuated in heterozygous (20% effective dose; 2 x 10-6 M) and homozygous klotho mice (> 1 x 10-5 M) as compared with wild-type mice (1 x 10-7 M, n = 7, p < 0.05). Nitric oxide metabolites (NO2- and NO3-) in urine are significantly lower in heterozygous klotho mice (142 ± 16 nmol/day) than wild-type mice (241 ± 28 nmol/day, n = 13, p < 0.05). Parabiosis between wild-type and heterozygous klotho mice results in restoration of endothelial function in heterozygous klotho mice. We conclude that the klotho protein protects the cardiovascular system through endothelium-derived NO production by humoral pathways.

Original languageEnglish (US)
Pages (from-to)324-329
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume248
Issue number2
DOIs
StatePublished - Jul 20 1998

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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