Contribution of TLR's/Inflammasome NLRP3/IL-1B axis in renal Ischemia/Reperfusion-induced electrophysiological disturbances

• Grant number: 17/05974-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2017
• End date: January 31, 2019
• Field of knowledge: Biological Sciences - Biophysics - Biophysics of Processes and Systems
• Principal Investigator: Marcela Sorelli Carneiro Ramos
• Grantee: Maria Micaela Lopez Alarcon
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Patients with chronic renal ischemia have a high risk to develop cardiovascular diseases. These diseases represent a 41% of death in patient in hemodialysis treatment. Therefore, understand the physiopathological mechanisms involved is critical. Recently, a study conducted by the proponent of the present project showed an elevated concentration of IL-1² 8 days after renal ischemia-reperfusion in mice. This finding was associated with longer QTc in these animals. On the other hand, in 2016, the candidate demonstrated the important role played by the macrophages IL-1² released in cardiac electrical remodeling. These effects were observed after toll like receptor (TLR's) 2 and NLRP3 inflammosome activation in these cells. Thus, the aim of this present project is to test the hypothesis that the activation of TLR's/ NLRP3 Inflammosome axis and IL-1² release by macrophages could be involved in renal ischemia/reperfusion-induced cardiac electrical alterations in mice. Preliminary data from Marcela's Laboratory showed that the lack of NLRP3 (NLRP3-/-) or caspase-1 (Casp-1-/-) 8 days post renal ischemia-reperfusion prevented both: i) the QTc prolongation and ii) the high systemic IL-1² concentration. In addition, other data showed that removal macrophages (with clodronate liposome) was enough to prevent the QTc prolongation 8 days after renal ischemia reperfusion. These data taken together also support our hypotheses in order to develop this propose. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LOPEZ ALARCON, MARIA MICAELA; TRENTIN-SONODA, MAYRA; PANICO, KARINE; SCHLEIER, YGOR; DUQUE, THABATA; MORENO-LOAIZA, OSCAR; DE YURRE, AINHOA RODRIGUEZ; FERREIRA, FABIANNO; CAIO-SILVA, WELLINGTON; COURY, PEDROSA ROBERTO; et al. Cardiac arrhythmias after renal I/R depend on IL-1 beta. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, v. 131, p. 101-111, JUN 2019. (08/10175-4, 17/05974-4)