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

• Published in: Cellular and molecular life sciences : CMLS Vol. 57; no. 5; pp. 738 - 746
• Main Authors: Nagai, R, Saito, Y, Ohyama, Y, Aizawa, H, Suga, T, Nakamura, T, Kurabayashi, M, Kuroo, M
• Format: Journal Article
• Language: English
• Published: Switzerland Springer Nature B.V 01.05.2000; Birkhäuser Verlag
• Subjects: Acetylcholine - pharmacology; Aging; Animal models; Animals; Aorta - drug effects; Aorta - physiopathology; Disease Models, Animal; Down-Regulation; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Glucuronidase; Heterozygote; Humans; Hyperlipidemias - genetics; Hyperlipidemias - physiopathology; Hypertension; Hypertension - genetics; Hypertension - physiopathology; In Vitro Techniques; Kidneys; Klotho Proteins; Male; Membrane Proteins - genetics; Membrane Proteins - physiology; Metabolic disorders; Metabolites; Mice; Mice, Knockout; Nitric Oxide - biosynthesis; Nitroprusside - pharmacology; Parabiosis; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Renal Insufficiency - genetics; Renal Insufficiency - physiopathology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Vasodilation - drug effects; Vasodilation - genetics; Vasodilation - physiology
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s000180050038

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.