Resumen:
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 d...