Key words.klotho; endothelial function; nitric oxide production; hypertension; renal failure; cytokine.
Springer Online Journal Archives 1860-2000
Abstract. The human aging process is associated with vascular endothelial dysfunction. However, humoral factors which might protect against endothelial dysfucntion 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.
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