Endothelial dysfunction in the klotho mouse and downregulation of klotho gene expression in various animal models of vascular and metabolic diseases

R. Nagai, Y. Saito, Y. Ohyama, H. Aizawa, T. Suga, T. Nakamura, M. Kurabayashi, M. Kuro-O

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)738-746
Number of pages9
JournalCellular and Molecular Life Sciences
Volume57
Issue number5
DOIs
StatePublished - Jul 1 2000

Keywords

  • Cytokine
  • Endothelial function
  • Hypertension
  • Klotho
  • Nitric oxide production
  • Renal failure

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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