Downregulation of interleukin-6 and C-reactive protein underlies a novel inhibitory role of microRNA-136-5p in acute lower extremity deep vein thrombosis

Aging (Albany NY). 2020 Nov 14;12(21):21076-21090. doi: 10.18632/aging.103140. Epub 2020 Nov 14.

Abstract

Deep vein thrombosis (DVT) comprises a critical and common health condition with high incidence, mortality, and long-term adverse sequelae. Several differentially expressed microRNAs (miRNAs) have emerged as promising prognostic markers in DVT. The present study intended to explore the functional relevance of miR-136-5p in acute lower extremity DVT (LEDVT). Rat models of acute LEDVT were established and miR-136-5p expression was altered by agomir or antagomir to assess its effects. In addition, in vitro gain- and loss-experiments, prior to exposure to CoCl2, were performed to investigate effects of miR-136-5p on human umbilical vein endothelial cell (HUVEC) apoptosis and levels of interleukin-6 (IL-6) and C-reactive protein (CRP). miR-136-5p was downregulated, whereas IL-6 and CRP were elevated in acute LEDVT patients. Notably, miR-136-5p was confirmed to target both IL-6 and CRP. Overexpression of miR-136-5p led to reduced length, weight, and ratio of weight to length of the venous thrombus. Furthermore, overexpressed miR-136-5p downregulated the expression of IL-6 and CRP, consequently inhibiting HUVEC apoptosis. Conjointly, our data indicate that the overexpression of miR-136-5p has the potential to bind to the 3'-UTR in the mRNAs for IL-6 and CRP and mitigate acute LEDVT, which provides a basis for new therapeutic targets in acute LEDVT treatment.

Keywords: acute lower extremity deep vein thrombosis; interleukin-6; microRNA-136-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • C-Reactive Protein / metabolism*
  • Down-Regulation
  • Female
  • Humans
  • Interleukin-6 / metabolism*
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Rats, Sprague-Dawley
  • Venous Thrombosis / metabolism*

Substances

  • IL6 protein, human
  • Interleukin-6
  • MIRN136 microRNA, human
  • MicroRNAs
  • C-Reactive Protein