Long noncoding RNA NEAT1/microRNA-125a axis predicts increased major adverse cardiac and cerebrovascular event risk independently in patients with unprotected left main coronary artery disease underwent coronary artery bypass grafting.

BACKGROUND: The study aimed to investigate the long noncoding RNA nuclear-enriched abundant transcript 1 (lnc-NEAT1) and microRNA-125a (miR-125a) expressions, and further explore the role of lnc-NEAT1/miR-125a axis in predicting major adverse cardiac and cerebrovascular event (MACCE) risk in patients with unprotected left main coronary artery disease (ULMCAD) underwent coronary artery bypass grafting (CABG). METHODS: A total of 280 patients with ULMCAD underwent CABG were consecutively enrolled in our prospective study, and their plasma samples were collected before CABG for the detection of lnc-NEAT1 and miR-125a expressions by reverse transcription quantitative polymerase chain reaction. Lnc-NEAT1/miR-125a axis was calculated via dividing lnc-NEAT1 by miR-125a. After CABG, regular follow-up was continued until MACCE occurrence or 36 months. RESULTS: Lnc-NEAT1 expression, miR-125a expression, and lnc-NEAT1/miR-125a axis were 0.998 (IQR: 0.440-1.720, range: 0.116-5.771), 0.997 (IQR: 0.461-1.650, range: 0.055-3.621), and 1.018 (IQR: 0.384-2.782, range: 0.041-52.832), respectively. And lnc-NEAT1 was negatively associated with miR-125a. The 1-, 2-, and 3-year MACCE occurrence was 19 (6.8%), 29 (10.4%), and 38 (13.6%), respectively. Lnc-NEAT1/miR-125a axis (χ2  = 11.207, P = .001) and lnc-NEAT1 expression (χ2  = 5.345, P = .021) positively associated with accumulating MACCE occurrence, while miR-125a expression (χ2  = 5.869, P = .015) negatively correlated with accumulating MACCE occurrence. Notably, lnc-NEAT1/miR-125a axis presented numerically better predictive value compared with lnc-NEAT1 or miR-125a alone for MACCE risk. Furthermore, lnc-NEAT1/miR-125a axis high, elderly age, increased BMI, diabetes, previous stroke, LVEF, and higher disease extent (all P < .05) were independent predictive factors for increased accumulating MACCE occurrence. CONCLUSION: Lnc-NEAT1/miR-125a axis, as a combined index, presents potential value to be a prognostic biomarker for MACCE risk in ULMCAD management.

Downregulation of microRNA-512-3p enhances the viability and suppresses the apoptosis of vascular endothelial cells, alleviates autophagy and endoplasmic reticulum stress as well as represses atherosclerotic lesions in atherosclerosis by adjusting spliced/unspliced ratio of X-box binding protein 1 (XBP-1S/XBP-1U).

AS is an important pathological basis of cardiovascular disease. miRNAs are involved in almost all steps of AS, including the injury and dysfunction of endothelial cells and vascular smooth muscle cells. This work elucidated the biological functions of miR-512-3p in AS and probed into the underlying molecular mechanism. In the present work, ox-LDL-treated HUVECs served as the in vitro model of AS and ApoE-/- mice were nourished with a high-fat diet to establish an in vivo model of AS. Proliferation, apoptosis, and migration of HUVECs were evaluated by CCK-8, TUNEL staining, Western blot, and transwell assays. Immunofluorescence examined LC3 expression and levels of autophagy-related and ER stress-related proteins were determined by Western blot assay. In addition, starBase predicted the complementary binding sites of XBP-1 to miR-512-3p and luciferase reporter assay confirmed the interaction between miR-512-3p and XBP-1. Moreover, H&E staining was employed to evaluate atherosclerotic lesions in AS model mice. Results revealed that ox-LDL treatment decreased the proliferative and migrative activities and promoted the apoptosis of HUVECs as well as induced autophagy and ER stress, which were abrogated by miR-512-3p silencing. Importantly, ox-LDL treatment elevated miR-512-3p expression and XBP-1 was a direct target of miR-512-3p. Mechanistically, knockdown of miR-512-3p enhanced the viability, suppressed the apoptosis, and promoted the migration of ox-LDL-treated HUVECs, alleviated atherosclerotic lesions in AS model mice as well as repressed autophagy and ER stress by targeting XBP-1 to manipulate the ratio of XBP-1S/XBP-1 U.

Atorvastatin combined with routine therapy on HIF-1, VEGF concentration and cardiac function in rats with acute myocardial infarction.

Effect of atorvastatin combined with routine therapy on the expression of hypoxia inducible factor (HIF-1) and vascular endothelial growth factor (VEGF) in rats with acute myocardial infarction (AMI) and its therapeutic effect were investigated. The rat models of acute myocardial infarction were established and divided into routine therapy, study, model, single drug and control group according to the treatment plan, with 10 cases in each group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentration of HIF-1 and VEGF in serum of rats before treatment (T0), and 3 days (T1), 5 days (T2) and 7 days (T3) after treatment, and the cardiac function was measured at the same time. The concentrations of HIF-1 and VEGF in serum of the study group and the routine therapy group after treatment were significantly higher than those before treatment. The concentrations of HIF-1 and VEGF in serum of model group at T0 were significantly lower than those at T3 (P<0.05). After treatment, the concentrations of HIF-1 and VEGF in serum of the study group were significantly higher than those of the routine therapy, the model and the control group (P<0.05). One week after administration, there were significant differences in the left ventricular function among the five groups (P<0.001). The left ventricular function in the study group was better than that in the routine therapy, model and control group. The levels of HIF-1 and VEGF in the serum of rats with myocardial infarction were negatively correlated with LVIDs and LVIDd, and positively correlated with LVEF% and LVFS%. In conclusion, atorvastatin combined with routine therapy can better reduce serum HIF-1 and VEGF levels and improve the left ventricular function in rats than routine therapy.

Effects of ubiquitin-proteasome inhibitor on the expression levels of TNF-α and TGF-ß1 in mice with viral myocarditis.

Effects of ubiquitin-proteasome system (UPS) inhibitor MG-132 on the expression levels of tumor necrosis factor-α (TNF-α) and transforming growth factor-ß1 (TGF-ß1) in mice with viral myocarditis were investigated to analyze the correlation of myocardial tissue score of mice between TNF-α and TGF-ß1. Eighty healthy male SPF mice aged 6 weeks were selected and 20 mice were randomly selected as the blank group. The blank group did not receive any intervention. Mortality rates of each group were recorded and compared on day 8 of modeling, and heart specimens from the remaining mice were histopathologically examined and the expression of mRNA and protein of TNF-α and TGF-ß1 in myocardial tissues were detected by western blot analysis. Correlation between mouse myocardial histopathologic scores and expression of protein of TNF-α and TGF-ß1 in myocardial tissues, as well as the expression of TNF-α and TGF-ß1 in myocardial tissue in VMC mice was analyzed. The expression levels of myocardial histopathological scores, mRNA and protein of TNF-α and TGF-ß1 in the blank and control group were significantly lower than those in the VMC and the MG-132 group. The myocardial histopathological scores, mRNA and TNF-α and TGF-ß1 protein in the MG-132 group were significantly lower than those in the VMC group (P<0.05). The expression of TNF-α and TGF-ß1 protein in myocardial tissues was positively correlated with the pathological score in myocardial tissue of mice (r=0.843, P<0.05; r=0.763, P<0.05), and there was a positive correlation between the expression of TNF-α and TGF-ß1 protein in myocardial tissues of VMC mice (r=0.672, P<0.05). UPS inhibitor MG-132, which can significantly alleviate the myocardial injury of VMC mice, reduced the expression of inflammatory factors in myocardial tissues, and improved the survival rate of mice, thus it is a potential new treatment for VMC.