MiR-126 prevents hypoxic HUVEC cellular injury through targeting TRAF6 expression.

Abstract

Aim: This study aimed to determine the clinical impact of miR-126 in identifying the severity of atherosclerotic CAD patients and its protective molecular mechanism against hypoxic exposed human umbilical vein endothelial cells (HUVEC) injury.

Methods: 124 multivessel blocked CAD patients, 87 double vessels stenosed CAD subjects, single vessel occluded 50 CAD patients, age and gender-matched 50 healthy individuals, and hypoxic-induced human umbilical vein endothelial cells were enrolled in this study. Quantitative real-time PCR (qRT-PCR) was used for the detection of relative miRNAs and mRNAs expressions and the severity of CAD patients was determined by the ROC analysis.

Results: Circulating plasma miR-126 expressions were greatly reduced in multivessel CAD patients as compared with the single and dual vessel as well as healthy subjects. Significantly expressed plasma miR-126 was also observed within single and multivessel CAD patients. Multivessel, double vessel, and single vessel atherosclerotic blocked CAD patients were highly distinguished from healthy volunteer participants with remarkable specificity and sensitivity and exhibited a prominent AUC of 0.940, 0.937, and 0.908 respectively. The relative expressions of miR-126 were comparatively lower in hypoxic induced HUVEC than in normal atmospheric cultured cells. Moreover, the expressions of LDH, caspase- 3 activities, ROS, and TRAF6 have significantly upregulated in hypoxic exposed HUVEC. In contrast, overexpression of miR-126 evidently reduced ROS production, LDH secretion, caspase-3 activities, and TRAF6 protein levels, and markedly elevated HUVEC cellular viability under hypoxic stress conditions.

Conclusions: Down-regulated plasma miR-126 acts as a newer universal clinical biomarker for the early detection and grading of CAD patients. Mimic expression of miR-126 significantly enhanced HUVEC cellular viability via targeting TRAF6 protein expression under hypoxic-induced inflammatory conditions, suggesting a newer molecular target for atherosclerotic CAD patients.