Febuxostat Protects Human Aortic Valve Endothelial Cells From Oxidized Low-density Lipoprotein-Induced Injury and Monocyte Attachment.

ABSTRACT: Atherosclerosis (AS) is a common cardiovascular disease with high morbidity and mortality. The pathogenesis of AS is closely related to endothelial dysfunction, which is mainly induced by oxidative stress, inflammation, and enhanced adhesion of monocytes to endothelial cells on the vessel wall. Febuxostat is a novel antigout agent recently reported to exert protective effects on endothelial dysfunction. This study aims to investigate the protective capacity of febuxostat against oxidized low-density lipoprotein (ox-LDL)-induced injury and monocyte attachment to endothelial cells. Human aortic valve endothelial cells (HAVECs) were stimulated with ox-LDL in the presence or absence of febuxostat (5 and 10 µM) for 6 hours. Mitochondrial reactive oxygen species were measured using MitoSox red staining, and the level of protein carbonyl was detected using enzyme-linked immunosorbent assay (ELISA). The expressions of IL-6, TNF-α, tissue factor (TF), VCAM-1, and ICAM-1 were evaluated with qRT-PCR assay and ELISA. Calcein-AM staining was used to determine the attachment of U937 monocytes to HAVECs. quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blot were used to measure the expression level of early growth response 1 (Egr-1) in HAVECs. First, the elevated expression of LOX-1, activated oxidative stress, excessive secreted inflammatory factors, and promoted expression of TF induced by stimulation with ox-LDL were significantly reversed by febuxostat, indicating a protective effect of febuxostat against endothelial dysfunction. Second, the upregulated VCAM-1 and ICAM-1, as well as the increased proportion of adhered monocytes to HAVECs induced by ox-LDL, were significantly alleviated by febuxostat. Finally, the promoted expression level of Egr-1 induced by ox-LDL was pronouncedly suppressed by febuxostat. We conclude that febuxostat protected HAVECs from ox-LDL-induced injury and monocyte attachment.

CoO Nanoparticles Combined with MRI: Analysis of No-Reflow in Patients with Acute ST-Segment Elevation Myocardial Infarction after PCI and the Effect of Coronary Nicorandil.

Magnetic resonance imaging (MRI) has become one of the most important medical imaging techniques in the clinic due to its high degree of soft tissue resolution and no radiation damage, and it plays an important role in the early diagnosis and treatment of tumors. This article mainly studies the analysis of no-reflow in patients with acute ST-segment elevation myocardial infarction after PCI and the effect of coronary nicorandil on CoO nanoparticles combined with MRI. In this paper, the synthesized water-soluble nanoparticles are dispersed in a 2% xanthan gum or agarose solution. In an MRI analyzer, the T1 value is tested with the inversion recovery sequence, and the T2 value is tested with the hard pulse CPMG sequence. The gyroscope imaging sequence performs T1-weighted and T2-weighted imaging tests. Calculated densitometry (QCA) was used to measure the stenosis of the coronary lesions, the length of the lesions and the diameter of the lumen before stent implantation. In order to facilitate the collection of urine samples, this article adopts the method of inserting a catheter to drain the patient for sampling. From the baseline state at the time of enrollment to 150 minutes after PCI, polyethylene containing 0.1% butylated hydroxyanisole is used. Urine samples were taken from the test tube every 30 minutes, a total of 6 times were collected, and the collected urine samples were stored in a low-temperature refrigerator at -80℃ for the final inspection. This paper uses calculation software to calculate the risk of death and death/myocardial infarction in the hospital and at 6 months after discharge. The data showed that the postoperatively detected CKMB and cTnI were higher than those before the operation, but the peak value of the nicorandil group was lower than that of the control group, but there was still no statistical difference (P>0.05). The results show that nicorandil can significantly improve the no-reflow phenomenon in AMI patients during PCI.

[Retracted] Rosuvastatin suppresses platelet­derived growth factor­BB­induced vascular smooth muscle cell proliferation and migration via the MAPK signaling pathway.

[This retracts the article DOI: 10.3892/etm.2013.1265.].

Geriatric nutritional risk index was associated with in-hospital mortality among cardiac intensive care unit patients.

Background: Identifying risk factors associated with cardiac intensive care unit (CICU) patients' prognosis can help clinicians intervene earlier and thus improve their prognosis. The correlation between the geriatric nutrition risk index (GNRI), which reflects nutritional status, and in-hospital mortality among CICU patients has yet to be established. Method: The present study retrospectively enrolled 4,698 CICU patients. Based on the nutritional status, the participants were categorized into four groups. The primary endpoint was in-hospital mortality. The length of hospital stay and length of CICU stay were the secondary endpoints. To explore the correlation between nutritional status and in-hospital mortality, a logistic regression analysis was conducted. The nonlinear associations of GNRI with in-hospital mortality were evaluated using restricted cubic spline (RCS). Furthermore, subgroup analyses were conducted to evaluate the effect of the GNRI on in-hospital mortality across different subgroups, with calculation of the p for interaction. Result: A higher risk of malnutrition was significantly linked to an increased incidence of in-hospital mortality (High risk vs. No risk: 26.2% vs. 4.6%, p < 0.001), as well as a longer length of hospital stay (High risk vs. No risk: 15.7, 9.1-25.1 vs. 8.9, 6.9-12.9, p < 0.001) and CICU stay (High risk vs. No risk: 6.4, 3.8-11.9 vs. 3.2, 2.3-5.1, p < 0.001). An elevated GNRI was significantly associated with an increased risk of in-hospital mortality even after controlling for pertinent confounding factors (High risk vs. No risk: OR, 95% CI: 2.37, 1.67-3.37, p < 0.001, p for trend <0.001). Additionally, the RCS model showed a linear relationship between GNRI and in-hospital mortality, with the risk of in-hospital mortality significantly decreasing as GNRI increased (non-linear p = 0.596). Furthermore, in the subgroups of hypertension, ventricular arrhythmias, cardiac arrest, shock, and chronic kidney disease, there was a significant interaction between nutritional status and in-hospital mortality. Conclusion: Among CICU patients, a low GNRI was a significant predictor of in-hospital mortality. Furthermore, patients with a higher risk of malnutrition, as indicated by low GNRI values, experienced significantly longer hospital and CICU stays.

Safety of Bivalirudin Combined with Ticagrelor in the Emergency PCI in Patients with Acute ST-Segment Elevation Myocardial Infarction.

OBJECTIVE: The present study aimed to investigate the application safety of bivalirudin combined with ticagrelor in the emergency percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: From October 1, 2018, to December 30, 2019, 210 patients with STEMI admitted to the Department of Cardiology who underwent emergency PCI were randomly divided into the bivalirudin group (group A, N = 105) and the unfractionated heparin group (group B, N = 105). Before the emergency PCI operation after admission, the loading dose of aspirin (300 mg) was given orally, and then 100 mg/d. At the same time, the loading dose of ticagrelor (180 mg) was administered orally, and then 90 mg/bid. The adverse events and the hemorrhage events 30 days after the operation were observed and recorded. RESULTS: There were five hemorrhage cases in the bivalirudin group, with one case of secondary hemorrhage and four cases of mild hemorrhage. There were 14 hemorrhages in the unfractionated heparin group with one case of secondary hemorrhage and thirteen cases of mild hemorrhage. In terms of mild hemorrhage, the hemorrhage rate in the bivalirudin group was significantly lower than that in the unfractionated heparin group (3.8% vs. 12.4%, P = 0.040). One patient died in the unfractionated heparin group, while no deaths occurred in the bivalirudin group during the thirty days of follow-up. No myocardial infarction, revascularization, or stroke occurred in the two groups within 30 days after the operation. CONCLUSION: Compared with unfractionated heparin combined with ticagrelor in patients with STEMI undergoing emergency PCI treatment, bivalirudin combined with ticagrelor could significantly reduce the occurrence of mild hemorrhage events, and it would not increase the incidence of MACE during the 30 days of follow-up.

The efficacy and safety of edoxaban versus warfarin in preventing clinical events in atrial fibrillation: A systematic review and meta-analysis.

Atrial fibrillation (AF) is the most common type of arrhythmia. Warfarin reduces the incidence and mortality of strokes in patients with AF. Edoxaban reduces the bleeding risk in patients with AF. This study evaluates the efficacy and safety of edoxaban versus warfarin in preventing clinical events in patients with AF through a meta-analysis of randomized controlled trials (RCTs). RCTs were retrieved from medical literature databases. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated to compare the primary and safety endpoints. In total, five articles (10 trial comparisons) containing 24,836 patients were retrieved. Of these patients, 16,268 (65.5%) received edoxaban and 8,568 (34.5%) received warfarin. Compared with warfarin, edoxaban significantly reduced the incidence of cardiovascular death (CVD), major bleeding, and non-major bleeding (RR: 0.86, 95% CI: 0.80-0.93, I2 : 0.0%; RR: 0.65, 95% CI: 0.59-0.71, I2 : 75.6%; and RR: 0.80, 95% CI: 0.77-0.84, I2 : 79.3%, respectively). Edoxaban did not increase the incidence of stroke, systemic embolic events, myocardial infarction, and adverse events compared with warfarin (RR: 1.00, 95% CI: 0.90-1.11, I2 : 42.8%; RR: 1.00, 95% CI: 0.67-1.49, I2 : 0.0%; RR: 1.08, 95% CI: 0.93-1.27, I2 : 0.0%; RR: 1.00, 95% CI: 0.91-1.10, I2: 46.4%, respectively). This meta-analysis indicated that compared with warfarin, edoxaban can significantly reduce the incidence of CVD and major and non-major bleeding. The anticoagulant effect and safety of edoxaban may be better than those of warfarin.

Latest Clinical Evidence About Effect of Acetylcysteine on Preventing Contrast-Induced Nephropathy in Patients Undergoing Angiography: A Meta-Analysis.

Contrast-induced nephropathy (CIN) is a serious complication of angiographic procedures. It is the third most common cause of hospital acquired acute renal injury. As there are currently no approved therapies for CIN, prevention could be the best strategy to address this issue. Acetylcysteine may indirectly play an antioxidant role by inducing the synthesis of glutathione. Acetylcysteine can also reduce renal vasoconstriction induced by contrast medium stimulation by stabilizing nitric oxide and acting directly or indirectly on renal cortex and medulla microcirculation. To evaluate the effect of acetylcysteine on the prevention of CIN in patients after angiography, we systematically searched and analyzed the clinical data of patients including the incidence of CIN and change in serum creatinine (SCr) at 48 hours after angiography from selected articles. The result showed that acetylcysteine significantly reduces the incidence of CIN (risk ratios: 0.78, 95% CI: 0.68-0.90, I2 = 37.3%) and the level of SCr (standardized mean difference: -0.53, 95% CI: -0.93 to -0.12, I2 = 91.5%) after angiography compared with the control group. Overall, the use of acetylcysteine in patients after angiography was associated with a significant reduction of CIN and the level of SCr.

Effect of intravenous application of nicorandil on area of myocardial infarction in patients with STEMI during the perioperative stage of PCI.

OBJECTIVE: The aim of the present study was to evaluate the effectiveness and safety of nicorandil in improving the area of myocardial infarction in patients with acute myocardial infarction (AMI). METHODS: One hundred and twenty patients with acute ST-segment elevation myocardial infarction (STEMI) admitted to our hospital between December 1, 2018 and December 31, 2019 were selected and randomly allocated to the experimental group (group A, n = 60) and the control group (group B, n = 60). In the experimental group, an infusion of nicorandil was given intravenously before the first balloon dilation or 1 minute before the stent placement, and with the completion of the infusion, nicorandil maintenance infusion was given. In the control group, only balloon dilation and stent placement were undertaken. RESULTS: The postoperative peak levels of myoglobin, creatine kinase isoform and hypersensitive troponin T were significantly lower in group A than in group B (p < 0.05). Moreover, the left ventricular ejection fraction (LVEF) on the 180th day post operation was substantially greater in group A than in group B (p < 0.01), and the area of myocardial infarction was significantly smaller in patients in group A than those in group B on the 180th day post operation (p < 0.01). In terms of the safety, there were no statistically significant differences in the incidence of slow flow/no reflow, malignant arrhythmias, and hypotension within 24 hours post operation between the two groups (p > 0.05), and no major adverse cardiovascular event (MACE) occurred in either group during the postoperative follow-up period of 180 days (p > 0.05). CONCLUSION: Intravenous administration of nicorandil in patients with STEMI during the perioperative percutaneous coronary intervention (PCI) period was effective in reducing the area of myocardial infarction and myocardial injury without increasing the incidence of malignant arrhythmias, hypotension, or composite cardiovascular events during the drug administration period.

The Efficacy And Safety Of Aspirin As The Primary Prevention Of Cardiovascular Disease: An Updated Meta-Analysis.

PURPOSE: Information regarding the use of aspirin for patients with no known cardiovascular disease remains conflicting. We performed an updated meta-analysis to evaluate the efficacy and safety of aspirin for primary prevention of cardiovascular disease. PATIENTS AND METHODS: PubMed, MEDLINE, and Cochrane library databases were searched for randomized controlled trials comparing aspirin with placebos or no treatment published up until November 1, 2018. The primary efficacy endpoint was all-cause death. The secondary endpoints included cardiovascular death, myocardial infarction, and stroke. The safety endpoints included major bleeding, gastrointestinal bleeding, and hemorrhagic stroke. RESULTS: Fourteen studies were included. Aspirin use was associated with a lower risk of myocardial infarction than placebo use or no treatment (risk ratio [RR], 0.83, 95% confidence interval [CI]: 0.73-0.95, P = 0.005). Additionally, compared with the control groups, aspirin use was not associated with a lower risk of all-cause mortality or cardiovascular mortality. In terms of safety, aspirin use was associated with a higher risk of major bleeding (RR, 1.40, 95% CI: 1.25-1.57, P = 0.000), gastrointestinal bleeding (RR, 1.58, 95% CI: 1.25-1.99, P = 0.000), and hemorrhagic stroke (RR, 1.30, 95% CI: 1.06-1.60, P = 0.011). Furthermore, the treatment effect was not significantly modified by patients' clinical characteristics. No publication bias was present. CONCLUSION: Aspirin use reduced the myocardial infarction risk in patients without known cardiovascular disease, but had no effect in terms of reducing the risk of all-cause death, cardiovascular death, and stroke, and increased the risk of major bleeding, gastrointestinal bleeding, and hemorrhagic stroke.

Rosuvastatin may reduce the incidence of cardiovascular events in patients with acute coronary syndromes receiving percutaneous coronary intervention by suppressing miR-155/SHIP-1 signaling pathway.

PURPOSE: The beneficial effect of rosuvastatin against percutaneous coronary intervention (PCI) related procedural myocardial injury has been determined mostly in patients with acute coronary syndromes (ACS). However, the detailed therapeutic mechanism has not been well studied. METHODS: Patients with ACS receiving PCI (n = 159) were randomized to control group (placebo treatment) or to rosuvastatin group (20 mg 12 h before PCI, and a further 20 mg 2 h preprocedure dose). Levels of INF-γ, TNF-α, IL-6, miR-155/SHIP-1, and CD4(+)FoxP3(+)Treg in peripheral blood were detected before PCI and 24 h after PCI. Clinical data of these patients were also collected in this prospective study. RESULTS: Compared with placebo, rosuvastatin treatment significantly reduced the incidence of periprocedural myocardial infarction (PMI) and levels of cardiac troponin I (cTnI) associated with decreased relative expression of serum miR-155, levels of inflammatory cytokines (INF-γ, TNF-α, and IL-6), increased SHIP-1 expression and CD4(+)FoxP3(+)Treg percentage values (P < 0.05). In addition, patients with rosuvastatin pretreatment also reduced incidence of 30 days major adverse cardiac events (MACE) compared to the patients with placebo treatment (16 patients vs. 28 patients, P = 0.038). CONCLUSIONS: Our study suggests that high loading dose rosuvastatin pretreatment may reduce the incidence of cardiovascular events and levels of inflammatory markers in patients with ACS receiving PCI, which may be explained at least in part, by mechanism involving suppression of miR-155/SHIP-1 signaling pathway.

Rosuvastatin suppresses platelet-derived growth factor-BB-induced vascular smooth muscle cell proliferation and migration via the MAPK signaling pathway.

An imbalance in the proliferation and migration of vascular smooth muscle cells (VSMCs) is significant in the onset and progression of vascular diseases, including arteriosclerosis and restenosis subsequent to vein grafting or coronary intervention. Rosuvastatin, a selective inhibitor of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase, has pharmacological properties including the ability to reduce low-density lipoprotein-cholesterol (LDL-C) and very low-density lipoprotein-cholesterol (VLDL-C) levels, slow atherosclerosis progression and improve coronary heart disease outcomes. However, little is known concerning the molecular mechanism by which rosuvastatin affects vascular cell dynamics. In this study, we studied the inhibitory role of rosuvastatin on platelet-derived growth factor-BB (PDGF-BB)-induced VSMC proliferation and migration, as well as the molecular mechanisms involved. MTT data showed that rosuvastatin markedly inhibited the proliferation of PDGF-BB-induced VSMCs in a time-dependent manner. VSMCs are able to dedifferentiate into a proliferative phenotype in response to PDGF-BB stimulation; however, rosuvastatin effectively attenuated this phenotype switching. Moreover, we also showed that rosuvastatin significantly suppressed PDGF-BB-induced VSMC migration, which may be a result of its inhibitory effect on the protein expression of matrix metalloproteinase-2 (MMP2) and MMP9. Investigation into the molecular mechanisms involved revealed that rosuvastatin inhibited the mitogen-activated protein kinase (MAPK) signaling pathway by downregulating extracellular signal-regulated kinase (ERK) and p38 MAPK, although the phosphorylation level of c-Jun N-terminal kinase (c-JNK) was not altered following rosuvastatin treatment. In conclusion, the present study showed that rosuvastatin suppressed PDGF-BB-induced VSMC proliferation and migration, indicating that rosuvastatin has the potential to become a promising therapeutic agent for the treatment of atherosclerosis and restenosis.