Abstract
Sepsis, the third most common cause of death worldwide, is associated with myocardial depression, one of the most common organ dysfunctions in sepsis. n this study, we found that miRNA-486 was significantly down-regulated in septic mice and miR-486 over-expression significantly up-regulated the IRE1/JNK pathway, resulting in increased autophagy and apoptosis. In our previous study, miR-486 has been shown to be a protective factor in sepsis overdose and the expression was significantly down-regulated, indicating that miR-486 is a sensitive responder in sepsis and may be an important indicator for the diagnosis and prognosis of sepsis. provided the first evidence that the expression of miR-486 in human macrophages (THP-1) was up-regulated after stimulation with lipopolysaccharide (LPS) (1 µg/mL). explored the expression profile of some miRNAs in bone marrow-derived macrophages (BMDMs) in LPS-induced sepsis mice using RT-PCR. The primary finding in our study is that in vivo over-expression of miR-486 depressed the myocardial function, and that miR-150 controlled the heart function in a constitutively negative manner. We had proved in SMs that miR-486 could repress Cav-1 expression, while miR-150 could inhibit calcineurin and l-type calcium channel. Calcium plays a fundamental role in the heart, and sepsis causing the imbalance of calcium ultimately leads to myocardial depression. Regulations of these related calcium signaling pathways also confirm and explain how miR-486 and miR-150 have a negative effect on myocardial function. These findings provide proof in mouse myocardial intramyocardial overexpression of miRs (miR-486, miR-150) in its decrease heart contractile function. Inconclusion, miR-486 and miR-150 play a protective role in sepsis-induced myocardial depression by inhibiting renin-angiotensin-aldosterone system dependent autophagy. This study may contribute to developing novel therapeutic strategies for favorably regulating miR-486 or miR-150 expression in sepsis-induced myocardial depression.
Keywords: Myocardial depression; Biomarkers; mRNA; Sepsis
Copyright © 2017 by The American Society for BioMedicine and BM-Publisher, Inc.
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https://doi.org/10.1038/nrg2484
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DOI: http://dx.doi.org/10.18081/2333-5106/015-06/313-324