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

Abstract

This study aimed to evaluate the role of eplerenone on the modulation of interleukin (IL)-1β 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-1β, 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-1β, 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-1β significantly. Both anakinra and eplerenone treatments were associated with lower levels of fibrosis and inflammatory markers. IL-1β could induce expression of sST2, accelerating the progression of heart failure after acute MI. Eplerenone could improve LV function by reducing expression of IL-1β and sST2.

• Authors: Bo Chen, Jing Geng, Shao-Xi Gao, Wen-Wei Yue, Qiang Liu
• Journal: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (J Interferon Cytokine Res) Vol. 38 Issue 3 Pg. 137-144 (03 2018) ISSN: 1557-7465 [Electronic] United States
• PMID: 29565745 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Il33 protein, rat
• Interleukin-1beta
• Interleukin-33
• Receptors, Interleukin-1
• ST2 protein, rat
• Eplerenone

Topics

• Acute Disease
• Animals
• Antihypertensive Agents (pharmacology)
• Eplerenone (pharmacology)
• Interleukin-1beta (deficiency, metabolism)
• Interleukin-33 (metabolism)
• Male
• Myocardial Infarction (drug therapy, metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, Interleukin-1 (deficiency, metabolism)
• Signal Transduction (drug effects)
• Ventricular Dysfunction, Left (drug therapy, metabolism)