Klotho protein protects against endothelial dysfunction - PubMed (original) (raw)

. 1998 Jul 20;248(2):324-9.

doi: 10.1006/bbrc.1998.8943.

T Yamagishi, T Nakamura, Y Ohyama, H Aizawa, T Suga, Y Matsumura, H Masuda, M Kurabayashi, M Kuro-o, Y Nabeshima, R Nagai

Affiliations

Klotho protein protects against endothelial dysfunction

Y Saito et al. Biochem Biophys Res Commun. 1998.

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 (NO-2 and NO-3) 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.

Copyright 1998 Academic Press.

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