Abstract
BackgroundAcute coronary syndrome (ACS) is a serious type of cardiovascular diseases. This study aimed to investigate the expression patterns and clinical value of microRNA-145 (miR-145) in ACS patients, and further uncover the function of miR-145 in ACS rats.MethodsQuantitative real-time PCR was used to estimate the expression of miR-145. Diagnostic value of miR-145 was evaluated, and its correlation with endothelial injury marker (vWF and H-FABP) and pro-inflammatory cytokines (IL-6 and TNF-α) was analyzed. Coronary artery ligation was adopted to construct the ACS rat model, and the effects of miR-145 on endothelial injury, inflammation and vascular endothelial cells (VECs) biological function were examined.ResultsDownregulated expression of miR-145 was found in the ACS serum samples compared with the healthy controls. The expression of miR-145 was proved to be a diagnostic biomarker and negatively correlated with vWF, H-FABP, IL-6 and TNF-α. The similar serum expression trends of miR-145 in ACS patients were also observed in the ACS rats, and the overexpression of miR-145 could decrease the elevated vWF, H-FABP, IL-6 and TNF-α in the animal model. Moreover, the upregulation of miR-145 in VECs led to promoted proliferation and migration. The bioinformatics prediction data and luciferase report results indicated that FOXO1 was a direct target of miR-145.ConclusionsIn conclusion, it was hypothesized that serum decreased expression of miR-145 may serve as a potential diagnostic biomarker in ACS patients. Overexpression of miR-145 may improve the endothelial injury and abnormal inflammation through targeting FOXO1, indicating that miR-145 serves as a candidate therapeutic target of ACS.
Highlights
Acute coronary syndrome (ACS) is a serious type of cardiovascular diseases
Diagnostic accuracy of miR‐145 in the patients with ACS Since an obvious decrease in miR-145 expression was found in ACS patients, we further evaluate the diagnostic ability of miR-145 to distinguish the ACS patients from the healthy individuals
The comparison results indicated that there was no significant difference between the two groups in age, gender, history of hypertension and smoking, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL), but more patients with dyslipidemia were found in ACS group compared with healthy controls (P = 0.022), and the creatine kinase MB mass (CK-MB mass), myoglobin (Myo) and cardiac troponin of ACS patients were higher than that of healthy controls
Summary
This study aimed to investigate the expression patterns and clinical value of microRNA-145 (miR-145) in ACS patients, and further uncover the function of miR-145 in ACS rats. To improve the endothelial injury and balance the inflammatory response in ACS, this study presented an investigation about the protective role of microRNA-145 (miR-145) in this disease. Overexpression of miR-330 has a protective effect on ACS by regulating the formation of atherosclerotic plaques and vascular endothelial cell proliferation [7]. The differentially expressed miR-145 was closely related with the progression of acute Kawasaki disease, which has great potential to develop into ACS [13]. The regulatory role of miR-145 in cell proliferation and inflammatory response has been reported in some other diseases [14, 15]. The clinical significance and functional role of miR-145 in ACS remain elusive
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