Klotho protects against indoxyl sulphate-induced myocardial hypertrophy

Ke Yang, Cheng Wang, Ling Nie, Xiaohui Zhao, Jun Gu, Xu Guan, Song Wang, Tangli Xiao, Xinli Xu, Ting He, Xuefeng Xia, Junping Wang, Jinghong Zhao

Research output: Contribution to journalArticle

86 Scopus citations

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=20.59, 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=20.49, 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 ofCKDmicewith 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.

Original languageEnglish (US)
Pages (from-to)2434-2446
Number of pages13
JournalJournal of the American Society of Nephrology
Volume26
Issue number10
DOIs
StatePublished - Oct 1 2015

ASJC Scopus subject areas

  • Nephrology

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