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

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 or in mice could prevent cardiac Ca mishandling induced by sixth nephrectomy (Nx), a model of CKD. We examined intracellular Ca dynamics in cardiomyocytes from (), and sham-operated or nephrectomized mice. Compared with cardiomyocytes, -Nx cells showed an impairment in the properties and kinetics of the intracellular Ca transients, a reduction in both cell shortening and sarcoplasmic reticulum Ca load, together with an increase in diastolic Ca leak. Cardiomyocytes from -Nx and -Nx mice showed a significant amelioration in Ca mishandling without modifying the kidney impairment induced by Nx. In conclusion, and deficiency prevents the intracellular Ca 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.