In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 34, No. 4 ( 2014-04), p. 857-869
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/ATVBAHA.113.303001
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2014
detail.hit.zdb_id:
1494427-3
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