The present study aimed to measure the levels of microRNA-381 (miR-381) in the plaque tissues, peripheral blood mononuclear cells (PBMCs) and serum of patients with coronary atherosclerosis. In addition, the regulatory mechanisms of miR-381 and cyclooxygenase (COX)-2 in coronary atherosclerosis were investigated. A total of 36 patients with coronary atherosclerosis who received coronary endarterectomy at Linyi People's Hospital and Junan Hospital of Traditional Chinese Medicine (Linyi, China) between January 2013 and June 2016 were enrolled into the present study, while 39 healthy subjects were included as the control group. Peripheral blood was collected form all patients and healthy subjects. Plaque tissues were resected from patients with coronary atherosclerosis and adjacent artery intimal tissues were resected as the control tissues. Using quantitative polymerase chain reaction, the levels of miR-381 and COX-2 mRNA in the plaque tissues, PBMCs and serum were determined. In addition, COX-2 protein expression in the plaque tissues and PBMCs was measured by western blotting, while enzyme-linked immunosorbent assay was utilized to examine the protein content in the serum. To identify the direct interaction between miR-381 and COX-2 mRNA, dual-luciferase reporter assay was also conducted. The levels of COX-2 mRNA and protein in the plaque tissues, PBMCs and serum of patients with coronary atherosclerosis were significantly elevated compared with those in the corresponding control groups. However, the expression of miR-381 was significantly reduced in the coronary atherosclerosis patients. Dual-luciferase reporter assay revealed that miR-381 was able to directly target the 3'-untranslated region of COX-2 mRNA to regulate the expression of COX-2. Therefore, the present study demonstrated that enhanced levels of COX-2 expression in patients with coronary atherosclerosis are associated with the downregulation of miR-381 expression, while miR-381 may regulate the occurrence and immune responses of coronary atherosclerosis via COX-2.

ObjectiveOver the years, the roles of microRNAs (miRNAs) and histone deacetylase 3 (HDAC3) in human diseases have been investigated. This study focused on the effect of miR‐19a‐3p and HDAC3 in myocardial ischemia–reperfusion (I/R) injury (MIRI) by targeting cyclin‐dependent kinase 2 (CDK2).MethodsThe I/R rat models were established by coronary artery ligation, which were then treated with RGFP966 (an inhibitor of HDAC3), miR‐19a‐3p agomir or antagomir, or silenced CDK2 to explore their roles in the cardiac function, pathological changes of myocardial tissues, myocardial infarction area, inflammatory factors and oxidative stress factors in rats with MIRI. The expression of miR‐19a‐3p, HDAC3, and CDK2 was determined by RT‐qPCR and western blot assay, and the interaction among which was also verified by online prediction, luciferase activity assay and ChIP assay.ResultsThe results indicated that HDAC3 and CDK2 were upregulated while miR‐19a‐3p was downregulated in myocardial tissues of I/R rats. The inhibited HDAC3/CDK2 or elevated miR‐19a‐3p could promote cardiac function, attenuate pathological changes, inflammatory reaction, oxidative stress, myocardial infarction area and apoptosis of myocardial tissues. HDAC3 mediates miR‐19a‐3p and CDK2 is targeted by miR‐19a‐3p.ConclusionInhibited HDAC3 ameliorates MIRI in a rat model by elevating miR‐19a‐3p and reducing CDK2, which may contribute to the treatment of MIRI.