ABSTRACT
Atherosclerosis (AS) is a chronic inflammatory disease characterized by the formation of atherosclerotic plaque in the intima of arteries. Among the known regulators of atherosclerosis, microRNAs (miRNAs) have been reported to play critical roles in lipoprotein homeostasis and plaque formation. But the roles of microRNA-125a-3p (miR-125a-3p) in the pathogenesis of AS remain unknown. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) to construct the vascular injury model of AS pathogenesis in vitro. miR-125a-3p and BMP and activin membrane-bound inhibitor (BAMBI) expression levels in HUVECs were then measured by quantitative real-time polymerase chain reaction and western blot. The viability and apoptosis of HUVECs were analyzed by Cell Counting Kit-8 assay, TUNEL assay, and flow cytometry, respectively. The relationship between BAMBI 3'-untranslated region and miR-125a-3p was validated by dual luciferase reporter gene assay. miR-125a-3p expression was raised in HUVECs induced with ox-LDL. In HUVECs, miR-125a-3p enhanced the effects of ox-LDL treatment on repressing the viability and promoting the apoptosis of cells. Additionally, BAMBI was confirmed as a direct target of miR-125a-3p and BAMBI overexpression reversed the effects of miR-125a-3p on HUVECs. miR-125a-3p aggravates the dysfunction of HUVECs induced by ox-LDL via BAMBI, which implies that miR-125a-3p is involved in the pathogenesis of AS.
Subject(s)
Atherosclerosis , Human Umbilical Vein Endothelial Cells , Lipoproteins, LDL , Membrane Proteins , MicroRNAs , Humans , Apoptosis/genetics , Apoptosis/physiology , Atherosclerosis/genetics , Atherosclerosis/metabolism , Cell Proliferation/genetics , Cell Proliferation/physiology , Human Umbilical Vein Endothelial Cells/metabolism , Human Umbilical Vein Endothelial Cells/pathology , Lipoproteins, LDL/genetics , Lipoproteins, LDL/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism , MicroRNAs/genetics , MicroRNAs/metabolismABSTRACT
BACKGROUND: Brain-derived neurotrophic factor (BDNF) regulates the lipid metabolism, atherosclerosis plaque formation, and inflammatory process, while the study about its clinical role in coronary heart disease (CHD) is few. The present study intended to explore the expression of BDNF and its relationship with stenosis, inflammation, and adhesion molecules in CHD patients. METHODS: After serum samples were obtained from 207 CHD patients, BDNF, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, IL-6, IL-8, IL-17A, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) levels were determined using ELISA. Then, the BDNF level was also examined in 40 disease controls (DCs) and 40 healthy controls (HCs), separately. RESULTS: BDNF was lower in CHD patients than in DCs and HCs (median (95% confidential interval) value: 5.6 (3.5-9.6) ng/mL vs. 10.7 (6.1-17.0) ng/mL and 12.6 (9.4-18.2) ng/mL, both p < 0.001). BDNF could well distinguish CHD patients from DCs (area under the curve [AUC]: 0.739) and HCs (AUC: 0.857). BDNF was negatively associated with triglyceride (p = 0.014), total cholesterol (p = 0.037), and low-density lipoprotein cholesterol (p = 0.008). BDNF was negatively associated with CRP (p < 0.001), TNF-α (p < 0.001), IL-1ß (p = 0.008), and IL-8 (p < 0.001). BDNF was negatively related to VCAM-1 (p < 0.001) and ICAM-1 (p = 0.003). BDNF was negatively linked with the Gensini score (p < 0.001). CONCLUSION: BDNF reflects the lipid dysregulation, inflammatory status, and stenosis degree in CHD patients.
