Cardiac arrhythmias after renal I/R depend on IL-1β
| Autor: | Pedrosa Roberto Coury, Wellington Caio-Silva, Karine Panico, Ygor Schleier, Thabata Duque, Fabianno Ferreira, Ainhoa Rodriguez de Yurre, Oscar Moreno-Loaiza, Marcela Sorelli Carneiro-Ramos, Emiliano Medei, Claudia N. Paiva, Maria Micaela Lopez Alarcon, Mayra Trentin-Sonoda |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Interleukin-1beta chemistry.chemical_element Renal function Cardiorenal syndrome 030204 cardiovascular system & hematology Calcium 03 medical and health sciences Mice 0302 clinical medicine Renal injury In vivo Internal medicine NLR Family Pyrin Domain-Containing 3 Protein medicine Animals Molecular Biology business.industry Caspase 1 Antagonist Arrhythmias Cardiac medicine.disease Immunity Innate Mice Inbred C57BL Electrophysiology 030104 developmental biology chemistry Reperfusion Injury cardiovascular system Cardiology Kidney Diseases Cardiology and Cardiovascular Medicine business Perfusion Signal Transduction |
| Zdroj: | Journal of molecular and cellular cardiology. 131 |
| ISSN: | 1095-8584 |
| Popis: | 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-1β 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-1β, 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 15 days 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-1β peak (at 7 days 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 15 days 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-1β is produced after sensing renal injury through NRLP3-CASP1, and IL-1β 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. |
| Databáze: | OpenAIRE |
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