| Full text | |
| Author(s): Show less - |
Lopez Alarcon, Maria Micaela
[1]
;
Trentin-Sonoda, Mayra
[1]
;
Panico, Karine
[1]
;
Schleier, Ygor
[2]
;
Duque, Thabata
[2]
;
Moreno-Loaiza, Oscar
[2]
;
de Yurre, Ainhoa Rodriguez
[2]
;
Ferreira, Fabianno
[3]
;
Caio-Silva, Wellington
[1]
;
Coury, Pedrosa Roberto
[4]
;
Paiva, Claudia N.
[3]
;
Medei, Emiliano
[2, 5]
;
Carneiro-Ramos, Marcela Sorelli
[1]
Total Authors: 13
|
| Affiliation: | [1] Univ Fed ABC, Ctr Nat & Human Sci CCNH, Santo Andre, SP - Brazil
[2] Univ Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, Lab Cardioimmunol, Rio De Janeiro - Brazil
[3] Univ Fed Rio de Janeiro, Inst Microbiol, Rio De Janeiro - Brazil
[4] Univ Fed Rio de Janeiro, Clementino Fraga Filho Hosp, Rio De Janeiro - Brazil
[5] Univ Fed Rio de Janeiro, Natl Ctr Struct Biol & Bioimaging CENABIO, Rio de Janeiro - Brazil
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY; v. 131, p. 101-111, JUN 2019. |
| Web of Science Citations: | 1 |
| Abstract | |
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-1 beta 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-1 beta, 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 NIrp3(-/-) and Casp1(-/-) mice after renal I/R. Depletion of macrophages in vivo after I/R and a day before IL-1 beta 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-1 beta is produced after sensing renal injury through NRLP3-CASP1, and IL-1 beta 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. (AU) | |
| FAPESP's process: | 08/10175-4 - Impact of inflammatory response induced by acute renal ischemia in cardiac tissue |
| Grantee: | Marcela Sorelli Carneiro Ramos |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| FAPESP's process: | 17/05974-4 - Contribution of TLR's/Inflammasome NLRP3/IL-1B axis in renal Ischemia/Reperfusion-induced electrophysiological disturbances |
| Grantee: | Maria Micaela Lopez Alarcon |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |