In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 117, No. suppl_1 ( 2015-07-17)
Abstract:
Background: Sepsis-induced cardiac dysfunction is charactered by cardiac contractility dysfunction, myocardial inflammation and cardiac metabolism abnormal. Dysfunction of microRNAs (miRNAs, miRs) contributes to a variety of human diseases. However, their roles in sepsis-induced cardiac dysfunction are unclear. Methods and Results: Cardiac dysfunction was induced by E.coli lipopolysaccharide (LPS) administration in mice and 8 dysregulated miRNAs were identified by miRNA arrays. Among them, miR-21* was found to be increased most obviously as determined by quantitative reverse transcription polymerase chain reactions. Inhibition of miR-21* in vivo by antagomir attenuated the reduction of factional shortening (FS) and ejection fraction (EF) induced by LPS administration while forced over-expression of miR-21* in vivo by agomir accelerated LPS-induced cardiac dysfunction. Besides that, S100A8 and S100A9, two genes related to cardiac contractility were also found to be regulated in vivo by injection of miR-21* agomirs and antagomirs. Interestingly, cardiac inflammation indictors such as TNF-α and IL-6 and cardiac metabolism regulators including PPAR family, CD36, FATP, GLUT1, GLUT4, PDK4 were not changed by miR-21* in vivo. These data indicate that miR-21* controls sepsis-induced cardiac dysfunction by direct affecting cardiac contractility instead of cardiac inflammation and metabolism. SORBS2 was identified as a target gene of miR-21* and it was decreased by miR-21* agomir and increased by miR-21* antagomir in vivo. In consist with this, circulating levels of miR-21* were also increased in patients with sepsis compared with healthy controls. Conclusion: miR-21* controls sepsis-induced cardiac dysfunction by regulating SORBS2. Inhibition of miR-21* represents a novel therapeutic strategy for sepsis-induced cardiac dysfunction.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/res.117.suppl_1.88
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2015
detail.hit.zdb_id:
1467838-X
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