miR‑124‑3p regulates angiogenesis in peripheral arterial disease by targeting STAT3

Abstract

Peripheral arterial disease (Pad) is the third leading cause of cardiovascular morbidity worldwide, after coronary artery disease and stroke. as endogenous regulators of gene expression, micrornas (mirs) are implicated in the development and progression of various diseases, including types of cancer, autoimmune diseases and heart diseases. in the present study, the role of mir-124-3p in Pad was investigated. The reverse transcription-quantitative Pcr results indicated that the expression levels of mir-124-3p were significantly increased in the ischemic tissue of the hindlimb ischemia (Hli) model and in hypoxic human umbilical vein endothelial cells compared with the corresponding control groups. Proliferation, wound healing and tube formation assays demonstrated the inhibition of mir-124-3p on angiogenesis in vitro and the Hli model indicated the same function of mir-124-3p in vivo. a dual-luciferase reporter revealed STaT3 as the target of mir-124-3p. The expression levels of mir-124-3p in human blood were negatively correlated with ankle-brachial index, which is an index for the evaluation of the severity of Pad. collectively, the present study indicated that mir-124-3p was a critical regulator of angiogenesis in Pad, and a potential diagnostic, prognostic and therapeutic target for Pad.

The Role of Circulating Biomarkers in Peripheral Arterial Disease

“…Besides their potential as diagnostic biomarkers, miRNAs have also been associated with PAD severity. For example, circulating miR-210 and miR-124 appeared upregulated in PAD, and inversely correlated with claudication distance and ABI respectively [ 123 , 125 ]. Likewise, serum miR-27b and miR-130a were also increased in atherosclerosis obliterans patients and positively correlated with Fontaine stages [ 124 ].…”

miR-548j-5p regulates angiogenesis in peripheral artery disease

“…However, in order to realize this therapeutic approach, it is necessary to understand the mechanisms and the pathways involved for individual potential miRNAs. For example, miR-24-3p was reported to regulate angiogenesis by inhibition of the expression of STAT3 26 , a regulator of angiogenesis beyond inflammation 27 , and the expression of miR-24-3p in human blood was reported to be negatively correlated with the ankle brachial index (ABI) 26 .…”

Relationships between Indicators of Lower Extremity Artery Disease and miRNA Expression in Peripheral Blood Mononuclear Cells

“…Differentially expressed miRNAs were reported in various tissues of patients with LEAD and were proposed as potential candidates for biomarkers of this disease [ 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. Several circulating miRNAs have been shown to have potential for use as a diagnostic, prognostic, and therapeutic targets for peripheral atherosclerosis [ 28 , 37 , 38 , 39 , 40 ].…”

“…There is limited information about the relation between miRNA expression and clinical parameters of LEAD advancement, such as ABI, claudication distance, or Rutherford and Fontaine categories. In previous research, an increase in the expression level of miR-124-3p induced by ischemic conditions was negatively correlated with ABI [ 38 ]. Higher serum levels of miR-93 have previously been found to be positively associated with PAD severity measured by ABI scores [ 41 ].…”