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Genetic Deletion of NOD1 Prevents Cardiac Ca²⁺ Mishandling Induced by Experimental Chronic Kidney Disease.

ABSTRACT: Risk of cardiovascular disease (CVD) increases considerably as renal function declines in chronic kidney disease (CKD). Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) has emerged as a novel innate immune receptor involved in both CVD and CKD. Following activation, NOD1 undergoes a conformational change that allows the activation of the receptor-interacting serine/threonine protein kinase 2 (RIP2), promoting an inflammatory response. We evaluated whether the genetic deficiency of Nod1 or Rip2 in mice could prevent cardiac Ca²⁺ mishandling induced by sixth nephrectomy (Nx), a model of CKD. We examined intracellular Ca²⁺ dynamics in cardiomyocytes from Wild-type (Wt), Nod1^-/- and Rip2^-/- sham-operated or nephrectomized mice. Compared with Wt cardiomyocytes, Wt-Nx cells showed an impairment in the properties and kinetics of the intracellular Ca²⁺ transients, a reduction in both cell shortening and sarcoplasmic reticulum Ca²⁺ load, together with an increase in diastolic Ca²⁺ leak. Cardiomyocytes from Nod1^-/--Nx and Rip2^-/--Nx mice showed a significant amelioration in Ca²⁺ mishandling without modifying the kidney impairment induced by Nx. In conclusion, Nod1 and Rip2 deficiency prevents the intracellular Ca²⁺ mishandling induced by experimental CKD, unveiling new innate immune targets for the development of innovative therapeutic strategies to reduce cardiac complications in patients with CKD.

SUBMITTER: Gil-Fernandez M

PROVIDER: S-EPMC7700567 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Genetic Deletion of NOD1 Prevents Cardiac Ca<sup>2+</sup> Mishandling Induced by Experimental Chronic Kidney Disease.

Gil-Fernández Marta M Navarro-García José Alberto JA Val-Blasco Almudena A González-Lafuente Laura L Martínez José Carlos JC Rueda Angélica A Tamayo Maria M Morgado José Luis JL Zaragoza Carlos C Ruilope Luis Miguel LM Delgado Carmen C Ruiz-Hurtado Gema G Fernández-Velasco María M

International journal of molecular sciences 20201123 22

Risk of cardiovascular disease (CVD) increases considerably as renal function declines in chronic kidney disease (CKD). Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) has emerged as a novel innate immune receptor involved in both CVD and CKD. Following activation, NOD1 undergoes a conformational change that allows the activation of the receptor-interacting serine/threonine protein kinase 2 (RIP2), promoting an inflammatory response. We evaluated whether the genetic deficie ...[more]

PMID: 33238586

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Dataset Information

Genetic Deletion of NOD1 Prevents Cardiac Ca²⁺ Mishandling Induced by Experimental Chronic Kidney Disease.

Publications

Genetic Deletion of NOD1 Prevents Cardiac Ca<sup>2+</sup> Mishandling Induced by Experimental Chronic Kidney Disease.

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Genetic Deletion of NOD1 Prevents Cardiac Ca2+ Mishandling Induced by Experimental Chronic Kidney Disease.

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Genetic Deletion of NOD1 Prevents Cardiac Ca<sup>2+</sup> Mishandling Induced by Experimental Chronic Kidney Disease.

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OmicsDI is part of the ELIXIR infrastructure

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Genetic Deletion of NOD1 Prevents Cardiac Ca²⁺ Mishandling Induced by Experimental Chronic Kidney Disease.