Dataset Information

Enhanced Klotho availability protects against cardiac dysfunction induced by uraemic cardiomyopathy by regulating Ca²⁺ handling.

ABSTRACT:

Background and purpose

Klotho is a membrane-bound or soluble protein, originally identified as an age-suppressing factor and regulator of mineral metabolism. Klotho deficiency is associated with the development of renal disease, but its role in cardiac function in the context of uraemic cardiomyopathy is unknown.

Experimental approach

We explored the effects of Klotho on cardiac Ca²⁺ cycling. We analysed Ca²⁺ handling in adult cardiomyocytes from Klotho-deficient (kl/kl) mice and from a murine model of 5/6 nephrectomy (Nfx). We also studied the effect of exogenous Klotho supplementation, by chronic recombinant Klotho treatment, or endogenous Klotho overexpression, using transgenic mice overexpressing Klotho (Tg-Kl), on uraemic cardiomyopathy. Hearts from Nfx mice were used to study Ca²⁺ sensitivity of ryanodine receptors and their phosphorylation state.

Key results

Cardiomyocytes from kl/kl mice showed decreased amplitude of intracellular Ca²⁺ transients and cellular shortening together with an increase in pro-arrhythmic Ca²⁺ events compared with cells from wild-type mice. Cardiomyocytes from Nfx mice exhibited the same impairment in Ca²⁺ cycling as kl/kl mice. Changes in Nfx cardiomyocytes were explained by higher sensitivity of ryanodine receptors to Ca²⁺ and their increased phosphorylation at the calmodulin kinase type II and protein kinase A sites. Ca²⁺ mishandling in Nfx-treated mice was fully prevented by chronic recombinant Klotho administration or transgenic Klotho overexpression.

Conclusions and implications

Klotho emerges as an attractive therapeutic tool to improve cardiac Ca²⁺ mishandling observed in uraemic cardiomyopathy. Strategies that improve Klotho availability are good candidates to protect the heart from functional cardiac alterations in renal disease.

SUBMITTER: Navarro-Garcia JA

PROVIDER: S-EPMC7520447 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Dataset Information

Enhanced Klotho availability protects against cardiac dysfunction induced by uraemic cardiomyopathy by regulating Ca²⁺ handling.

Background and purpose

Experimental approach

Key results

Conclusions and implications

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Enhanced Klotho availability protects against cardiac dysfunction induced by uraemic cardiomyopathy by regulating Ca2+ handling.

Background and purpose

Experimental approach

Key results

Conclusions and implications

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Enhanced Klotho availability protects against cardiac dysfunction induced by uraemic cardiomyopathy by regulating Ca²⁺ handling.