First Author | Alarcon MML | Year | 2019 |
Journal | J Mol Cell Cardiol | Volume | 131 |
Pages | 101-111 | PubMed ID | 31029578 |
Mgi Jnum | J:275922 | Mgi Id | MGI:6305005 |
Doi | 10.1016/j.yjmcc.2019.04.025 | Citation | Alarcon MML, et al. (2019) Cardiac arrhythmias after renal I/R depend on IL-1beta. J Mol Cell Cardiol 131:101-111 |
abstractText | AIMS: Cardiac arrhythmias are one of the most important remote complications after kidney injury. Renal ischemia reperfusion (I/R) is a major cause of acute renal injury predisposing to several remote dysfunctions, including cardiac electrical disturbance. Since IL-1beta production dependent on NLRP3 represents a link between tissue malfunctioning and cardiac arrhythmias, here we tested the hypothesis that longer ventricular repolarization and arrhythmias after renal I/R depend on this innate immunity sensor. METHODS AND RESULTS: Nlrp3(-/-) and Casp1(-/-) mice reacted to renal I/R with no increase in plasma IL-1beta, different from WT (wild-type) I/R. A prolonged QJ interval and an increased susceptibility to ventricular arrhythmias were found after I/R compared to Sham controls in wild-type mice at 15days post-perfusion, but not in Nlrp3(-/-) or CASP1(-/-) I/R, indicating that the absence of NLRP3 or CASP1 totally prevented longer QJ interval after renal I/R. In contrast with WT mice, we found no renal atrophy and no renal dysfunction in Nlrp3(-/-) and Casp1(-/-) mice after renal I/R. Depletion of macrophages in vivo after I/R and a day before IL-1beta peak (at 7days post-perfusion) totally prevented prolongation of QJ interval, suggesting that macrophages might participate as sensors of tissue injury. Moreover, treatment of I/R-WT mice with IL-1r antagonist (IL-1ra) from 8 to 15days post perfusion did not interfere with renal function, but reversed QJ prolongation, prevented the increase in susceptibility to ventricular arrhythmias and rescued a close to normal duration and amplitude of calcium transient. CONCLUSION: Taken together, these results corroborate the hypothesis that IL-1beta is produced after sensing renal injury through NRLP3-CASP1, and IL-1beta on its turn triggers longer ventricular repolarization and increase susceptibility to cardiac arrhythmias. Still, they offer a therapeutic approach to treat cardiac arrhythmias that arise after renal I/R. |