MicroRNA-135b-5p Is a Pathologic Biomarker in the Endothelial Cells of Arteriovenous Malformations

Int J Mol Sci. 2024 Apr 30;25(9):4888. doi: 10.3390/ijms25094888.

Abstract

Arteriovenous malformations (AVMs) are congenital vascular anomalies with a poor prognosis. AVMs are considered intractable diseases, as there is no established approach for early diagnosis and treatment. Therefore, this study aimed to provide new evidence by analyzing microRNAs (miRNAs) associated with AVM. We present fundamental evidence for the early diagnosis and treatment of AVM by analyzing miRNAs in the endothelial cells of AVMs. This study performed sequencing and validation of miRNAs in endothelial cells from normal and AVM tissues. Five upregulated and two downregulated miRNAs were subsequently analyzed under hypoxia and vascular endothelial growth factor (VEGF) treatment by one-way analysis of variance (ANOVA). Under hypoxic conditions, miR-135b-5p was significantly upregulated in the AVM compared to that under normal conditions, corresponding to increased endothelial activity (p-value = 0.0238). VEGF treatment showed no significant increase in miR-135b-5p under normal conditions, however, a surge in AVM was observed. Under both hypoxia and VEGF treatment, comparison indicated a downregulation of miR-135b-5p in AVM. Therefore, miR-135b-5p was assumed to affect the pathophysiological process of AVM and might play a vital role as a potential biomarker of AVMs for application related to diagnosis and treatment.

Keywords: arteriovenous malformation; endothelial cells; microRNA-135b-5p.

MeSH terms

  • Adult
  • Arteriovenous Malformations* / diagnosis
  • Arteriovenous Malformations* / genetics
  • Arteriovenous Malformations* / metabolism
  • Arteriovenous Malformations* / pathology
  • Biomarkers*
  • Cell Hypoxia / genetics
  • Endothelial Cells* / metabolism
  • Endothelial Cells* / pathology
  • Female
  • Humans
  • Male
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Vascular Endothelial Growth Factor A* / genetics
  • Vascular Endothelial Growth Factor A* / metabolism

Substances

  • MicroRNAs
  • MIRN135 microRNA, human
  • Biomarkers
  • Vascular Endothelial Growth Factor A

Grants and funding

This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (No. 2023R1A2C2004906). This study was supported by the National Research Foundation (NRF) grants funded by the Korean government (2021R1A5A2021614).