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Biochem Biophys Res Commun. 2016 Mar 18;471(4):423-9. doi: 10.1016/j.bbrc.2016.02.065. Epub 2016 Feb 17.

MicroRNA-9 inhibits hyperglycemia-induced pyroptosis in human ventricular cardiomyocytes by targeting ELAVL1.

Author information

1
Department of Cardiovascular Sciences, Centre for Cardiovascular Regeneration, Houston Methodist Research Institute, Houston, TX 77030, USA.
2
Houston Methodist DeBakey Heart & Vascular Center, Houston Methodist Hospital, Houston, TX, USA.
3
Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA.
4
Department of Cardiovascular Sciences, Centre for Cardiovascular Regeneration, Houston Methodist Research Institute, Houston, TX 77030, USA; Cell and Developmental Biology, Department of Cardiothoracic Surgery, Weill Cornell Medical College of Cornell University, New York, NY, USA. Electronic address: pkrishnamurthy@houstonmethodist.org.

Abstract

Diabetic cardiomyopathy is a common complication in patients with diabetes and is associated with underlying chronic inflammation and cardiac cell death, subsequently leading to heart failure (HF). ELAV-like protein 1 (ELAVL1) plays a critical role in the progression of inflammation and HF. However the role of ELAVL-1 in inflammation induced cardiac cell death (pyroptosis) under hyperglycemic condition remains elusive. Our data demonstrates that ELAVL1 expression augmented with a concomitant increase in caspase-1 and IL-1 beta expression in human hearts and human ventricular cardiomyocytes under hyperglycemic condition. Furthermore, ELAVL1 knockdown abrogates TNF-α induced canonical pyroptosis via NLRP3, caspase-1 and IL-1beta suppression. Bioinformatics analysis and target validation assays showed that miR-9 directly targets ELAVL1. Interestingly, miRNA-9 expression significantly reduced in high glucose treated cardiomyocytes and in human diabetic hearts. Inhibition of miR-9 upregulates ELAVL1 expression and activates caspase-1. Alternatively, treatment with miR-9 mimics attenuates hyperglycemia-induced ELAVL1 and inhibits cardiomyocyte pyroptosis. Taken together our study highlights the potential therapeutic implications of targeting miR-9/ELAVL1 in preventing cardiomyocyte cell loss during HF in diabetics.

KEYWORDS:

Diabetic cardiomyopathy; ELAVL1; Inflammation; MicroRNA-9; Pyroptosis

PMID:
26898797
PMCID:
PMC4818978
DOI:
10.1016/j.bbrc.2016.02.065
[Indexed for MEDLINE]
Free PMC Article

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