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.
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