TY - JOUR
T1 - Klotho protein protects against endothelial dysfunction
AU - Saito, Yuichiro
AU - Yamagishi, Takahiro
AU - Nakamura, Tetsuya
AU - Ohyama, Yoshio
AU - Aizawa, Hiroki
AU - Suga, Tatsuo
AU - Matsumura, Yutaka
AU - Masuda, Hiroaki
AU - Kurabayashi, Masahiko
AU - Kuro-O, Makoto
AU - Nabeshima, Yo Ichi
AU - Nagai, Ryozo
N1 - Funding Information:
We thank S. Saiki for technical and secretarial assistance. This study was supported by the Program for Promotion of Fundamental Studies in Health Sciences of the Organization for Drug ADR Relief, R&D Promotion and Product Review of Japan, and Kimura Memorial Heart Foundation Grant for Research on Autonomic Nervous System and Hypertension.
PY - 1998/7/20
Y1 - 1998/7/20
N2 - 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.
AB - 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.
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U2 - 10.1006/bbrc.1998.8943
DO - 10.1006/bbrc.1998.8943
M3 - Article
C2 - 9675134
AN - SCOPUS:0032551734
SN - 0006-291X
VL - 248
SP - 324
EP - 329
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -