Abstract 88: Microrna-21* Controls Sepsis-induced Cardiac Dysfunction
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.
Author Disclosures: H. Wang: None. Y. Bei: None. J. Shi: None. W. Sun: None. H. Liu: None. X. Li: None. J. Xiao: None. X. Kong: None.
- © 2015 by American Heart Association, Inc.