Abstract
The human aging process is associated with vascular endothelial dysfunction. However, humoral factors which might protect against endothelial dysfunction during aging have not yet been identified. We recently identified the klotho gene as a possible regulator of human aging. In the present study using the klotho-deficient heterozygous mouse, we examined whether the Klotho protein is a humoral factor protecting against endothelial dysfunction. We further cloned rat klotho cDNA and investigated whether klotho mRNA expression in rat kidney is altered under pathological conditions such as hypertension, hyperlipidemia, renal failure, and inflammatory stress. The Klotho protein itself, or its metabolites, promotes endothelial NO production in aorta as well as arterioles, and klotho mRNA in kidney is downregulated under sustained circulatory stress.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholine / pharmacology
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Animals
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Aorta / drug effects
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Aorta / physiopathology
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Disease Models, Animal
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Down-Regulation
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / physiopathology*
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Glucuronidase
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Heterozygote
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Humans
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Hyperlipidemias / genetics
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Hyperlipidemias / physiopathology
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Hypertension / genetics
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Hypertension / physiopathology
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In Vitro Techniques
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Klotho Proteins
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Male
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Membrane Proteins / genetics*
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Membrane Proteins / physiology*
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Mice
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Mice, Knockout
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Nitric Oxide / biosynthesis
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Nitroprusside / pharmacology
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Parabiosis
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Inbred SHR
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Rats, Inbred WKY
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Renal Insufficiency / genetics
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Renal Insufficiency / physiopathology
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Vasodilation / drug effects
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Vasodilation / genetics
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Vasodilation / physiology
Substances
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Membrane Proteins
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RNA, Messenger
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Nitroprusside
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Nitric Oxide
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Glucuronidase
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Klotho Proteins
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Acetylcholine