Dysregulation of Vascular Endothelial Growth Factor Receptor-2 by Multiple miRNAs in Endothelial Colony-Forming Cells of Coronary Artery Disease

Shu Han Su, Chun Hsien Wu, Ya Lin Chiu, Shing Jyh Chang, Hung Hao Lo, Ko Hsun Liao, Cheng Fong Tsai, Tsung Neng Tsai, Chi Hung Lin, Shu Meng Cheng, Cheng Chung Cheng, Hsei Wei Wang

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Background/Aims: Endothelial colony-forming cells (ECFCs) have the potential to be used in regenerative medicine. Dysfunction of ECFCs is correlated with the onset of cardiovascular disorders, especially coronary artery disease (CAD). Binding of vascular endothelial growth factor A (VEGFA) to vascular endothelial growth factor receptor-2 (VEGFR2) triggers cell motility and angiogenesis of ECFCs, which are crucial to vascular repair. Methods: To identify the miRNA-VEGFR2-dependent regulation of ECFC functions, ECFCs isolated from peripheral blood of disease-free and CAD individuals were subjected to small RNA sequencing for identification of anti-VEGFR2 miRNAs. The angiogenic activities of the miRNAs were determined in both in vitro and in vivo mice models. Results: Three miRNAs, namely miR-410-3p, miR-497-5p, and miR-2355-5p, were identified to be upregulated in CAD-ECFCs, and VEGFR2 was their common target gene. Knockdown of these miRNAs not only restored the expression of VEGFR2 and increased angiogenic activities of CAD-ECFCs in vitro, but also promoted blood flow recovery in ischemic limbs in vivo. miR-410-3p, miR-497-5p, and miR-2355-5p could serve as potential biomarkers for CAD detection as they are highly expressed in the plasma of CAD patients. Conclusions: This modulation could help develop new therapeutic modalities for cardiovascular diseases and other vascular dysregulated diseases, especially tumor angiogenesis.

Original languageEnglish
Pages (from-to)22-32
Number of pages11
JournalJournal of Vascular Research
Volume54
Issue number1
DOIs
StatePublished - 1 Apr 2017

Keywords

  • Coronary artery disease
  • Endothelial cells
  • microRNA

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