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Klotho protein protects against endothelial dysfunction
Y Saito1, T Yamagishi, T Nakamura
1Second Department of Internal Medicine, Gunma University School of Medicine, 3-39-22 Showa, Maebashi, Gunma, 371-8511, Japan.
Insights
Klotho protein protects the cardiovascular system by enhancing nitric oxide (NO) production. This circulating factor is crucial for maintaining endothelial function and preventing age-related arteriosclerosis.
Area of Science:
- Cardiovascular Biology
- Endocrinology
- Aging Research
Background:
- Arteriosclerosis, linked to aging, is a major cardiovascular disease risk factor.
- Klotho mice exhibit age-related disorders, including arteriosclerosis.
- The role of klotho protein as a circulating factor and its effect on endothelial function remain unclear.
Purpose of the Study:
- To investigate the endothelial function in klotho mice.
- To determine the physiological role of klotho protein as a circulating factor.
- To elucidate the mechanism by which klotho protein influences cardiovascular health.
Main Methods:
- Assessment of aortic and arteriolar vasodilator responses to acetylcholine in wild-type, heterozygous, and homozygous klotho mice.
- Measurement of urinary nitric oxide metabolites (NO-2 and NO-3).
- Parabiosis experiments between wild-type and heterozygous klotho mice.
Main Results:
- Heterozygous klotho mice showed significantly reduced aortic relaxation response to acetylcholine compared to wild-type mice.
- Vasodilator response of arterioles to acetylcholine was significantly attenuated in heterozygous and homozygous klotho mice.
- Urinary nitric oxide metabolites were significantly lower in heterozygous klotho mice.
- Parabiosis restored endothelial function in heterozygous klotho mice.
Conclusions:
- Klotho protein plays a protective role in the cardiovascular system.
- This protection is mediated through endothelium-derived nitric oxide (NO) production via humoral pathways.
- Klotho protein is a crucial circulating factor for maintaining vascular health and preventing age-related cardiovascular decline.
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.