title: Klotho upregulation by rapamycin protects against vascular disease in CKD.
abstract: Medial arterial calcification involves chondrogenic/osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Zhao et al. report that phosphate activates the mammalian target of rapamycin (mTOR) cascade in VSMCs, leading to downregulation of Klotho. Furthermore, rapamycin was shown to halt medial calcification. This effect was blunted in the absence of Klotho. Given the concomitant anti-atherosclerotic effects of the mTOR inhibitor, this agent has clinical potential as an inhibitor of intimal atherosclerosis and medial calcification.
authors.affiliation: Department of Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hamano
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects*; D001013:Aorta, Thoracic / Q000187:drug effects*; D001018:Aortic Diseases / Q000517:prevention & control*; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D061205:Vascular Calcification / Q000517:prevention & control*
chemical_list: D047428:Protein Kinase Inhibitors; D058570:TOR Serine-Threonine Kinases; D005966:Glucuronidase; D020123:Sirolimus