Deficiency of the MicroRNA-31-MicroRNA-720 pathway in the plasma and endothelial progenitor cells from patients with coronary artery disease

Hsei Wei Wang, Tse Shun Huang, Hung Hao Lo, Po Hsun Huang, Chih Ching Lin, Shing Jyh Chang, Ko Hsun Liao, Chin Han Tsai, Chia Hao Chan, Cheng Fong Tsai, Yi Chieh Cheng, Ya Ling Chiu, Tsung Neng Tsai, Cheng Chung Cheng, Shu Meng Cheng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

Objective-Defects in angiogenesis/vasculogenesis or vessel repair are major complications of coronary artery disease (CAD). Endothelial progenitor cells (EPCs) play a fundamental role in postnatal vascular repair and CAD. The role of microRNAs in CAD pathogenesis and their potential as biomarkers remain to be elucidated. Approach and results-MicroRNA-31 (miR-31) level in both the plasma and EPCs of patients with CAD is found lower. miR-31 regulates EPC activities by targeting FAT atypical cadherin 4 and thromboxane A2 receptor, which show increased expression in CAD EPCs. Overexpressing miR-31 in CAD EPCs rescued their angiogenic and vasculogenic abilities both in vitro and in vivo. When exploring approaches to restore endogenous miR-31, we found that far-infrared treatment enhanced the expression of not only miR-31, but also miR-720 in CAD EPCs. miR-720, which was also decreased in EPCs and the plasma of patients with CAD, stimulated EPC activity by targeting vasohibin 1. The miR720-vasohibin 1 pair was shown to be downstream of FAT atypical cadherin 4, but not of thromboxane A2 receptor. FAT atypical cadherin 4 inhibited miR-720 expression via repression of the planar cell polarity signaling gene four-jointed box 1 (FJX1), which was required for miR-720 expression through a hypoxia-inducible factor 1, α subunit-dependent mechanism. Restoring miR-720 level strengthened activity of CAD EPCs. The miR-31-miR-720 pathway is shown critical to EPC activation and that downregulation of this pathway contributes to CAD pathogenesis. Circulating levels of miR-31, miR-720, and vasohibin 1 have the potential to allow early diagnosis of CAD and to act as prognosis biomarkers for CAD and other EPC-related diseases. Conclusions-Manipulating the expression of the miR-31-miR-720 pathway in malfunction EPCs should help develop novel therapeutic modalities.

Original languageEnglish
Pages (from-to)857-869
Number of pages13
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume34
Issue number4
DOIs
StatePublished - Apr 2014

Keywords

  • coronary artery disease
  • microRNAs

Fingerprint

Dive into the research topics of 'Deficiency of the MicroRNA-31-MicroRNA-720 pathway in the plasma and endothelial progenitor cells from patients with coronary artery disease'. Together they form a unique fingerprint.

Cite this