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

Prince Jeyabal, Rajarajan A. Thandavarayan, Darukeshwara Joladarashi, Sahana Suresh Babu, Shashirekha Krishnamurthy, Arvind Bhimaraj, Keith A. Youker, Raj Kishore, Prasanna Krishnamurthy

Research output: Contribution to journalArticle

47 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)423-429
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume471
Issue number4
DOIs
StatePublished - Mar 18 2016

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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