Eplerenone Modulates Interleukin-33/sST2 Signaling and IL-1 in Left Ventricular Systolic Dysfunction After Acute Myocardial Infarction

This study aimed to evaluate the role of eplerenone on the modulation of interleukin (IL)-1 and IL-33/sST2 signaling pathway in an experimental model of left ventricular (LV) systolic dysfunction after acute myocardial infarction (MI). MI rats were randomly assigned to no treatment (MI group, n=10), to receive eplerenone (Epl group, n=10), or anakinra (Ana group, n=10). LV function was assessed by echocardiography. IL-1, IL-33/sST2, and cardiac fibrosis biomarkers were analyzed by quantitative real-time reverse transcription polymerase chain reaction (PCR). Rats with MI showed significant reduction of LV systolic function, but treatment with eplerenone or anakinra improved left ventricular end-diastolic volume (LVEDV) and LVEDV/mass values. In the infarcted myocardium, compared with sham animals, the MI group had higher level of IL-33, sST2, and IL-1, as well as higher concentrations of markers of fibrosis and inflammation. Treatment with anakinra downregulated sST2 but with no effects on IL-33. Eplerenone reduced levels of sST2 and IL-1 significantly. Both anakinra and eplerenone treatments were associated with lower levels of fibrosis and inflammatory markers. IL-1 could induce expression of sST2, accelerating the progression of heart failure after acute MI. Eplerenone could improve LV function by reducing expression of IL-1 and sST2.