Genetic Deletion of NOD1 Prevents Cardiac Ca2+ Mishandling Induced by Experimental Chronic Kidney Disease.
Int J Mol Sci
; 21(22)2020 Nov 23.
Article
en En
| MEDLINE
| ID: mdl-33238586
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Insuficiencia Renal Crónica
/
Proteína Serina-Treonina Quinasa 2 de Interacción con Receptor
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Proteína Adaptadora de Señalización NOD1
/
Riñón
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Mol Sci
Año:
2020
Tipo del documento:
Article
País de afiliación:
España