Abstract
The aim of the study was to explore the clinical impact of circulatory miR-126 as a candidate for novel biomarker in patients with coronary artery disease (CAD) and its protective role against hypoxia/reoxygenation- (H/R-) exposed HUVEC cellular injury. A total of 278 subjects, which included 153 subjects with angiographically confirmed CAD, 70 unstable angina subjects, and 55 healthy individuals, along with 18-hour HR-induced HUVECs were recruited in this study. Plasma miR-126 levels were significantly downregulated in stable and unstable CAD patients as well as 18-hour HR-exposed HUVECs as compared with controls. Stable and unstable CAD subjects were significantly differentiated from healthy individuals with a predictive value of AUC 0.903 and 0.923, respectively. Moreover, peripheral circulatory miR-126 expressions in elderly (71-90 years) stable and unstable CAD patients were comparatively lower than younger (30-50 years) subjects. The caspase-3 activity, intracellular ROS concentrations, and cellular viabilities were evidently increased in 18-hour HR-exposed HUVECs than in normal cells (P < 0.001). On the contrary, mimic expressions of miR-126 prominently reduced caspase-3 activity and intracellular ROS levels and markedly enhanced HUVEC cellular viabilities (P < 0.001). LRP6 expressions were significantly elevated in HR-induced HUVECs, whereas overexpression of miR-126 remarkably decreased LRP6 expressions (P < 0.001). Plasma miR-126 could be used as a novel biomarker for early prediction of CAD subjects. Overexpression of miR-126 significantly improved HUVEC cellular viabilities by downregulation of LRP6 protein expression, suggesting a potential therapeutic target for CAD patients.
Highlights
Ischemic coronary artery disease (CAD) is a predominant cause of high morbidity and mortality among all the races in both genders all over the world
The current study investigated the clinical significance of circulating miR-126 in CAD patients, and its protective effects against hypoxia/ reoxygenation- (H/R-) induced Human umbilical vein endothelial cells (HUVECs) cellular injury and the underlying molecular mechanism linked with lipoprotein receptor-related protein 6 (LRP6)
History of coronary heart disease and hs-CRP levels were higher in CAD than control healthy individuals (P < 0:001)
Summary
Ischemic coronary artery disease (CAD) is a predominant cause of high morbidity and mortality among all the races in both genders all over the world. Detection of major risk factors, prompt diagnosis, and proper management can significantly decline morbidity and mortality [1]. Invasive coronary angiogram (CAG) has been widely used to confirm the diagnosis of atherosclerotic ischemic coronary heart disease, but it has some limitations in its availability and unsuitability for extremely senescent patients and cases of end-stage renal failure. In the 20th century, advanced percutaneous transluminal coronary angioplasty (PTCA) has become the treatment of choice for the CAD patients, yet multivessel lesions and complex left main coronary occlusion are not manageable by such a treatment modality. Coronary artery disease occurs mainly due to progressive chronic atherosclerotic inflammation in the coronary arteries. Several research groups have demonstrated that different atherosclerotic linked microRNAs (miR-217, miR-200c, miR-146a, miR-34a, miR-221, and miR-19b) have an essential role in terms of development and progression of coronary atherosclerosis [2,3,4]
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