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

• Published in: Aging (Albany, NY.) NY.), 2020-11, Vol.12 (21), p.21076-21090
• Main Authors: Ou, Minghui, Hao, Shaobo, Chen, Jing, Zhao, Shibo, Cui, Shichao, Tu, Jie
• Format: Article
• Language: English
• Subjects: 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; Research Paper; Venous Thrombosis - metabolism
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.103140

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, gain- and loss-experiments, prior to exposure to CoCl , 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.