title: Klotho Protects Against Indoxyl Sulphate-Induced Myocardial Hypertrophy.
abstract: Left ventricular hypertrophy (LVH) is a common complication in patients with CKD and an independent risk factor for death. Changes in the levels of uremic solutes or Klotho have been reported to be related to CKD, whereas the relationships between these factors and CKD-associated LVH remain unclear. Here, we investigated the interaction between Klotho and indoxyl sulfate (IS), a typical uremic solute, in CKD-associated LVH. In a survey of 86 patients with CKD, a negative relationship was found between serum levels of IS and Klotho (r=-0.59, P<0.001). Furthermore, serum levels of IS and Klotho were independently associated with LVH (for IS: r=0.69, P<0.001; for Klotho: r=-0.49, P<0.001). In normal mice, intraperitoneal injection of IS for 8 weeks induced LVH accompanied by substantial downregulation of renal Klotho. Notably, IS-induced LVH was more severe in heterozygous Klotho-deficient (kl/+) mice. In vitro, treatment with Klotho strongly inhibited IS-induced cardiomyocyte hypertrophy by blocking oxidative stress and inhibiting p38 and extracellular signal-regulated protein kinase 1/2 signaling pathways. In a mouse model of CKD-associated LVH, the renal expression of Klotho was lower and the level of serum IS was higher than in healthy controls. Moreover, treatment of CKD mice with Klotho protein significantly restrained the development of LVH. Taken together, these results suggest that Klotho is an endogenous protector against IS-induced LVH, and the imbalance between Klotho and IS may contribute to the development of LVH in CKD.
authors: Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of People's Liberation Army, Xinqiao Hospital.
authors: Ke
authors: K
authors: Yang
authors: Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, and.
authors: Cheng
authors: C
authors: Wang
authors: Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of People's Liberation Army, Xinqiao Hospital.
authors: Ling
authors: L
authors: Nie
authors: Department of Cardiology, Xinqiao Hospital, Third Military Medical University, Chongqing, China;
authors: Xiaohui
authors: X
authors: Zhao
authors: State Key Laboratory of Protein and Plant Gene Research, College of Life Science, Peking University, Beijing, China; and.
authors: Jun
authors: J
authors: Gu
authors: Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of People's Liberation Army, Xinqiao Hospital.
authors: Xu
authors: X
authors: Guan
authors: Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, and.
authors: Song
authors: S
authors: Wang
authors: Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of People's Liberation Army, Xinqiao Hospital.
authors: Tangli
authors: T
authors: Xiao
authors: Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of People's Liberation Army, Xinqiao Hospital.
authors: Xinli
authors: X
authors: Xu
authors: Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of People's Liberation Army, Xinqiao Hospital.
authors: Ting
authors: T
authors: He
authors: Center for Genomic Medicine, Houston Methodist Research Institute, Houston, Texas.
authors: Xuefeng
authors: X
authors: Xia
authors: Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, and zhaojh@tmmu.edu.cn wangjunping@tmmu.edu.cn.
authors: Junping
authors: J
authors: Wang
authors: Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of People's Liberation Army, Xinqiao Hospital, zhaojh@tmmu.edu.cn wangjunping@tmmu.edu.cn.
authors: Jinghong
authors: J
authors: Zhao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D005260:Female; D005966:Glucuronidase / Q000097:blood / Q000502:physiology* / Q000627:therapeutic use; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000139:chemically induced / Q000209:etiology* / Q000517:prevention & control; D007200:Indican / Q000008:administration & dosage / Q000097:blood / Q000502:physiology*; D000090265:Klotho Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications*; D055815:Young Adult
chemical_list: D005966:Glucuronidase; D000090265:Klotho Proteins; D007200:Indican
keywords: CKD; left ventricular hypertrophy; uremia