Circ_0003575 knockdown alleviates ox-LDL-induced human aortic endothelial cell dysfunction in atherosclerosis by miR-637/TRAF6 axis.

BACKGROUND: Circular RNAs (circRNAs) are involved in the progression of atherosclerosis (AS). The present study aimed to determine the functions and mechanism of circ_0003575 in AS. METHODS: Oxidized low-density lipoprotein (ox-LDL) was used to induce human aortic endothelial cells (HAECs) to establish an AS cell model. Cell Counting Kit-8 (CCK-8) assay and 5'-ethynyl-2'-deoxyuridine (EdU) assay were conducted to assess cell proliferation. Flow cytometry analysis was utilized to quantify cell apoptosis. Tube formation assay was performed to analyze angiogenesis ability. Enzyme linked immunosorbent assay (ELISA) was used to examine the concentrations of inflammatory factors. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were manipulated for the expression of circ_0003575, microRNA-637 (miR-637) and TNF receptor associated factor 6 (TRAF6). Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were adopted to estimate the downstream targets of circ_0003575. RESULTS: Ox-LDL treatment repressed the proliferation and angiogenesis and promoted the apoptosis and inflammation in HAECs. Circ_0003575 knockdown ameliorated ox-LDL-induced injury of HAECs. Circ_0003575 interacted with mi-R-637, which directly targeted TRAF6. Inhibition of miR-637 reversed the impacts of circ_0003575 knockdown on HAEC injury. Moreover, miR-637 overexpression promoted cell proliferation and angiogenesis and inhibited cell apoptosis and inflammation by targeting TRAF6 in ox-LDL-treated HAECs. Further, circ_0003575 silencing inhibited the activation of NF-κB pathway. CONCLUSION: Circ_0003575 knockdown alleviated ox-LDL-induced HAEC damage by regulating miR-637/TRAF6 and NF-κB pathways.

Prognostic factors in young patients with ST-segment elevation myocardial infarction.

OBJECTIVE: The prognostic factors of young patients aged ≤40 years with ST-segment elevation myocardial infarction (STEMI) remain unclear. This study explored risk factors that may affect the 1-year prognosis of young STEMI patients by analyzing patient data of baseline, clinical regimen, and secondary prevention. METHODS: Baseline and clinical data were collected from 420 STEMI patients aged ≤40 years. One year of follow-up was performed to record and compare the differences in data between patients with and without adverse events. Binary logistic regression analysis with controls for confounding factors was used to evaluate prognosis-related independent factors. RESULTS: The overall incidence of cardiovascular adverse events was 15.95%. Comparison of the subgroups revealed that regardless of adjustment for confounding factors, prognoses of the patients were affected by the following factors: BMI, marital status, serum apolipoprotein(a) (ApoA) levels, number of diseased vessels, treatment regimen, compliance of secondary prevention, improvement of lifestyle, and adjusted comorbidities ( P  < 0.05). Independent analysis of adverse events revealed that BMI, number of diseased vessels, and compliance of secondary prevention were independent factors of recurrent acute myocardial infarction in patients. Serum ApoA level, treatment regimen, and compliance of secondary prevention were independent influence factors of heart failure in patients. Marital status and serum ApoA level were independent factors of malignant arrhythmias in patients. BMI, compliance of secondary prevention, and improvement of lifestyle were independent factors of cardiac death in patients. CONCLUSION: This study determined the influential factors for the prognosis of STEMI patients aged ≤40 years as follows: BMI, marital status, comorbidities, number of diseased vessels, regimen, compliance of secondary prevention, and improvement of lifestyle. The risk of cardiovascular adverse events may be reduced by modulating the influential factors.

L-ascorbic acid could ameliorate the damage of myocardial microvascular endothelial cell caused by hypoxia-reoxygenation via targeting HMGB1.

In this study, we intend to explore the potential function of l-ascorbic acid in hypoxia-reoxygenation (H/R)-induced damage of CMECs and its related molecular mechanism. With different concentrations of l-ascorbic acid treatment, the proliferation, migration, inflammation and autophagy of cardiac microvascular endothelial cells (CMECs) were determined by several biological experiments. Si-HMGB1 transfection was used to reduce HMGB1 expression and to detect the function of HMGB1 in H/R-induced damage of CMECs. Under H/R condition, the proliferation and migration abilities of CMECs were reduced, and the inflammation and autophagy of CMECs were increased. Whereas, after l-ascorbic acid treatment, the reduction in the proliferation and migration of CMECs, as well as the increase in the inflammation and autophagy of CMECs induced by H/R were reversely altered. HMGB1 was confirmed as a specific target of l-ascorbic acid, and si-HMGB1 treatment strengthened the beneficial effect of l-ascorbic acid on H/R-induced damage of CMECs, followed by further reduction in the proliferation and migration abilities of CMECs, as well as the increase in the inflammation and autophagy of CMECs. Few studies have reported the function of l-ascorbic acid in myocardial ischemia on CMECs, but our experimental data showed that l-ascorbic acid treatment could ameliorate the H/R-induced damage of CMECs by regulating HMGB1 expression.

MicroRNA-362-3p Implicated in Cardioprotection Against Hypoxia/Reoxygenation-Induced Cardiomyocyte Apoptosis by Repressing TP53INP2 and Regulating SDF-1/CXCR4 Pathway.

Objective: To investigate the role of miR-362-3p and its target in cardiomyocytes with hypoxia/reoxygenation (H/R) injury. Results: We found that miR-362-3p was decreased in myocardial infarction (MI) samples, and promoted the proliferation and restrained the apoptosis of H/R-injured H9c2 cells. TP53INP2 was recognized as the target of miR-362-3p and negatively modulated by miR-362-3p. Furthermore, the promotive effect of miR-362-3p on the proliferation of H/R-injured H9c2 cells was weakened by pcDNA3.1-TP53INP2, while the suppression on the apoptosis of H/R-injured H9c2 cells triggered by an miR-362-3p mimic was increased by pcDNA3.1-TP53INP2 by regulating apoptosis-associated proteins, as well as SDF-1 and CXCR4. Summary: miR-362-3p/TP53INP2 axis could ameliorate H/R-induced injury to cardiomyocytes by adjusting the SDF-1/CXCR4 signaling pathway.

The Application of Dopamine Combined with Intravenous Furosemide Infusion Therapy Has an Apparent Clinical Effect in Treating Patients with Heart Failure.

Objective: To observe the efficacy and safety of dopamine plus furosemide in treating patients with heart failure. Methods: This research included 150 patients with heart failure who were diagnosed and treated at our hospital between March 2018 and November 2020. The patients were randomly assigned to a study group or a reference group according to the data of admission (the cut-off date was June 2019). Patients in the reference group were given furosemide, whereas those in the study group were given dopamine plus furosemide intravenous pumping. Outcome measures included clinical effectiveness, heart function changes, and adverse responses. Results: Dopamine plus furosemide resulted in higher treatment efficiency (96.00%) versus furosemide (74.67%) study group (P < 0.05). Before therapy, there was no significant change in the scores of cardiac function indices between the two groups (P > 0.05). The cardiac function of the two groups of patients was improved after treatment, and the left ventricular ejection fraction (LVEF) of the study group (44.85 ± 4.12) was higher than that of the reference group (38.45 ± 4.36), and the left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVESD), and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) (43.17 ± 3.98, 51.32 ± 4.25, 3045.56 ± 365.48) were lower than the reference group (47.56 ± 4.65, 56.28 ± 4.85, 4856.48 ± 395.46) (P < 0.05). There was no significant difference in the total incidence of adverse reactions between the two groups (P > 0.05). Conclusion: Dopamine plus intravenous furosemide infusion treatment has an obvious therapeutic benefit in treating patients with heart failure and dramatically enhances cardiac function without noteworthy adverse responses. It demonstrated great potential for clinical promotion.

MiR-24 Protects Cardiomyocytes Against Hypoxia/Reoxygenation-Induced Injury Through Regulating Mitogen-Activated Protein Kinase 14.

This study aimed to explore the function of miR-24 in hypoxia/reoxygenation (H/R) -induced cardiomyocyte injury.We constructed a cardiomyocyte model of H/R using the primary cardiomyocytes isolated from Sprague-Dawley rats. To explore the role of miR-24, cells were transfected with a miR-24 mimic or miR-24 inhibitor. The RNA expression levels of miR-24 and Mapk14 were determined using qRT-PCR. The proliferation and apoptosis of cells were determined using a CCK8 assay and a flow cytometer. The TargetScan website was used to predict the targets of miR-24. A dual-luciferase reporter gene assay was conducted to verify whether Mapk14 is indeed a target of miR-24. A Western blot was applied for protein detection.H/R exposure decreased the expression of miR-24 in rat cardiomyocytes. Transfection of the miR-24 mimic into cardiomyocytes reduced H/R-induced injury as evidenced by an increase in proliferation and a decrease in the apoptotic rate. By contrast, transfection of the miR-24 inhibitor aggravated H/R-induced injury. The expression of Bcl-2 was increased while the levels of Bax and Active-caspase 3 were reduced in the H/R+miR-24 mimic group compared to those in the H/R group. H/R+miR-24 inhibitor group showed the opposite results. Mapk14 was identified as a target of miR-24. The mRNA level of Mapk14 and its protein (p38 MAPK) level were negatively affected by miR-24. Furthermore, we discovered that depletion of Mapk14 reduced the promoting effect of the miR-24 inhibitor on cell apoptosis.Overall, our results illustrated that miR-24 could attenuate H/R-induced injury partly by regulating Mapk14.