N­acetyl cysteine prevents ambient fine particulate matter­potentiated atherosclerosis via inhibition of reactive oxygen species­induced oxidized low density lipoprotein elevation and decreased circulating endothelial progenitor cell.

Ambient fine particulate matter (PM) serves an important role in the development of cardiovascular disease, including atherosclerosis. Antioxidant N­acetyl cysteine (NAC) has protective effects in the cardiovascular system. However, it is unknown if NAC prevents PM­potentiated atherosclerosis in hyperlipidemia. Low­density lipoprotein (LDL) receptor knockout mice were pretreated with 1 mg/ml NAC in drinking water for 1 week and continued to receive NAC, high­fat diet and intranasal instillation of PM for 1 week or 6 months. Blood plasma was collected for lipid profile, oxidized (ox­)LDL, blood reactive oxygen species (ROS) and inflammatory cytokine (TNF­α, IL­1ß and IL­6) measurement. Blood cells were harvested for endothelial progenitor cell (EPC) population and intracellular ROS analysis. Murine aorta was isolated for atherosclerotic plaque ratio calculation. NAC treatment maintained circulating EPC level and significantly decreased blood ox­LDL and ROS, inflammatory cytokines, mononuclear and EPC intracellular ROS levels as well as aortic plaque ratio. NAC prevented PM­potentiated atherosclerosis by inhibiting plasma ROS­induced ox­LDL elevation, mononuclear cell and EPC intracellular ROS­induced circulating EPC reduction and inflammatory cytokine production.

Differences in the reaction of hyperlipidemia on different endothelial progenitor cells based on sex.

The sex of a patient can affect the outcomes of several cardiovascular diseases, and men generally tend to experience earlier episodes of cardiovascular diseases compared with women. The progression of atherosclerosis during hyperlipidemia can be induced by reactive oxygen species (ROS) and oxidized-low-density lipoprotein (ox-LDL). By contrast, bone marrow (BM)-derived endothelial progenitor cells (EPCs) have been reported to serve a protective role against atherosclerosis. The aim of the present was to compare the effects of sex under conditions of hyperlipidemia on different populations of EPCs, and to identify the potential underlying mechanisms. EPC numbers and ROS levels in the blood and BM were measured using fluorescence activated cell sorting in male and female LDL receptor knock-out C57BL/6 mice maintained on a high-fat diet for 6 months, and in male and female wild type C57BL/6 mice following ox-LDL injection for 3 days. Female hyperlipidemic mice exhibited lower levels of plasma lipids, atherosclerotic plaque formation, intracellular EPC ROS formation and inflammatory cytokine levels. Furthermore, BM CD34+/ fetal liver kinase-1 (Flk-1+), CD34+/CD133+ and stem cell antigen-1+/Flk-1+, as well as all circulating EPCs, were maintained at higher levels in female hyperlipidemic mice. In addition, similar changes with regards to BM CD34+/Flk-1+, CD34+/CD133+, c-Kit+/CD31+ and circulating CD34+/Flk1+ and CD34+/CD133+ EPCs were observed in female mice following ox-LDL treatment. These sustained higher levels of BM and circulating EPCs in female mice with hyperlipidemia may be associated with reduced levels of ox-LDL as a result of reduced intracellular ROS formation in EPCs and decreased inflammatory cytokine production.

Value of S100A12 in predicting in-stent restenosis in patients with coronary drug-eluting stent implantation.

In-stent restenosis (ISR) after drug-eluting stent (DES) placement has recently emerged as a major concern for cardiologists. Identification of biomarkers to predict ISR may be invaluable for tailored management strategies. The present study aimed to evaluate the prognostic utility of circulating S100 calcium-binding protein A12 (S100A12) for ISR. Out of 2,443 patients with DES-based percutaneous coronary intervention (PCI) and follow-up angiography at ~1 year after DES-based PCI, 258 patients were diagnosed with ISR and 258 patients without ISR were randomly selected as controls. Serum S100A12 levels were determined in the two subsets on admission. The association between ISR and the circulating levels of S100A12 was determined by constructing two multivariate stepwise logistic regression models. In addition, S100A12 was assessed for its ability to predict ISR using receiver operating characteristic (ROC) curve analysis. The serum levels of S100A12 at baseline were significantly elevated in patients in the ISR group compared with those in the non-ISR group (P<0.001). In the multivariate logistic regression analysis, after adjusting for conventional cardiovascular risk factors, laboratory parameters and medication after the procedure, the S100A12 level was revealed to be independently associated with ISR. When a cut-off for serum S100A12 levels of 34.75 ng/ml was used, the ROC curve was able to predict ISR with 72.8% sensitivity and 79.1% specificity, and the area under the ROC curve was 0.796 (95% CI: 0.757 to 0.834, P<0.001). Furthermore, addition of S100A12 to established risk factors significantly improved the predictive power of reference models for ISR. S100A12 may serve as an independent marker to predict ISR in patients undergoing coronary DES implantation.

Probucol protects circulating endothelial progenitor cells from ambient PM2.5 damage via inhibition of reactive oxygen species and inflammatory cytokine production in vivo.

Bone marrow-derived circulating endothelial progenitor cells (EPCs) contribute to angiogenesis and vascular repair. The number and function of EPCs are significantly decreased following exposure to ambient fine particulate matter of ≤2.5 µm in diameter (PM2.5) through reactive oxygen species (ROS) generation and inflammatory cytokine secretion. The anti-oxidant drug probucol reduces ROS and inflammatory cytokine production. The present study was designed to determine the protective effects of probucol on EPCs from PM2.5-associated impairment in vivo and to explore the potential underlying mechanisms. Male C57BL/6 mice were exposed to ambient air containing PM2.5 for one month with or without probucol treatment. Mice that breathed filtered air were used as a control group. Serum and blood cells were collected for analysis. The results indicated that PM2.5 exposure induced increases in blood intracellular ROS, serum inflammatory cytokine levels and the blood cell apoptotic rate, while it decreased the number and proliferation rate of circulating EPCs in the mice with PM2.5 exposure. These effects were significantly reduced/abrogated by probucol treatment. The present in vivo study suggested that probucol protects EPCs from damage through PM2.5 exposure by inhibiting ROS generation and inflammatory cytokine production.

Efficacy and safety of combination therapy of chemoembolization and radiofrequency ablation with different time intervals for hepatocellular carcinoma patients.

BACKGROUND AND OBJECTIVES: Combination of transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) has become an effective alternative therapy for hepatocellular carcinoma (HCC). In clinical practice, the choice of time interval between TACE and RFA is a key point for curative effect, but optimal time interval is uncertain in guidelines. We aim to explore the optimal time interval for HCC patients of Child-Pugh classification A or B. METHODS: Two hundred and thirty-three HCC patients of Child A or B who had undergone TACE and RFA were enrolled and divided into seven groups according to different time intervals (1-7weeks). Tumor damage, liver function, complications and survival time of patients after treatment were analyzed. RESULTS: Complete remission rate and total effective rate decreased in groups with the prolonged time interval (p < 0.05). Average Child-Pugh score of patients in first three groups significantly increased one month after combination treatment (p < 0.01). While that not happened in other groups. Complications occurred in 16.7% patients, similarly occurred in groups (p > 0.1). Median survival time in groups four and five were 42 months, longer than other groups (p < 0.01). CONCLUSION: A period of 3-5 weeks is the optimal time interval between TACE and RFA for HCC patients of Child-Pugh classification A or B.

Spleen Stiffness Is Superior to Liver Stiffness for Predicting Esophageal Varices in Chronic Liver Disease: A Meta-Analysis.

BACKGROUND AND AIMS: Liver stiffness (LS) and spleen stiffness (SS) are two most widely accessible non-invasive parameters for predicting esophageal varices (EV), but the reported accuracy of the two predictors have been inconsistent across studies. This meta-analysis aims to evaluate the diagnostic performance of LS and SS measurement for detecting EV in patients with chronic liver disease (CLD), and compare their accuracy. METHODS: Pubmed/Medline, Embase, Cochrane Library and Ovid were searched for all studies assessing SS and LS simultaneously in EV diagnosis. A total of 16 studies including 1892 patients were included in this meta-analysis, and the pooled statistical parameters were calculated using the bivariate mixed effects models. RESULTS: In detection of any EV, for LS measurement, the summary sensitivity was 0.83 (95% confidence interval [CI]: 0.78-0.87), and the specificity was 0.66 (95% CI: 0.60-0.72). While for SS measurement, the pooled sensitivity and specificity was 0.88 (95% CI: 0.83-0.92) and 0.78 (95% CI: 0.73-0.83). The summary receiver operating characteristic (SROC) curve values of LS and SS were 0.81 (95% CI: 0.77-0.84) and 0.88 (95% CI: 0.85-0.91) respectively, and the results had statistical significance (P<0.01). The diagnostic odds ratio (DOR) of SS (25.73) was significantly higher than that of LS (9.54), with the relative DOR value was 2.48 (95%CI: 1.10-5.60), P<0.05. CONCLUSIONS: Under current techniques, SS is significantly superior to LS for identifying the presence of EV in patients with CLD. SS measurement may help to select patients for endoscopic screening.

Probucol Protects Endothelial Progenitor Cells Against Oxidized Low-Density Lipoprotein via Suppression of Reactive Oxygen Species Formation In Vivo.

BACKGROUND/AIMS: Oxidized low-density lipoprotein (ox-LDL) is a major component of hyperlipidemia and contributes to atherosclerosis. Endothelial progenitor cells (EPCs) play an important role in preventing atherosclerosis and notably decreased in hyperlipidemia. Ox-LDL and ox-LDL-related reactive oxygen species (ROS) have deleterious effects on EPCs. Probucol as an antioxidant and anti-inflammatory drug reduces ROS production. The present study was to determine if probucol could protect EPCs from ox-LDL in vivo and to investigate the potential mechanisms. METHODS: ox-LDL was injected into male C57BL/6 mice for 3 days with or without probucol treatment with PBS as control. Bone marrow (BM) fluid, serum, circulating mononuclear cells (MNCs) and EPCs were collected for analysis. RESULTS: the increased extracellular ROS in BM, serum and blood intracellular ROS production in the mice with ox-LDL treatment in association with a significant reduction of circulating MNCs and EPCs were restored with Probucol treatment. A significant increase in the serum ox-LDL and C-reactive protein and decrease in superoxide dismutase and circulating MNCs and EPCs were observed in hyperlipidemic patients that were effectively reversed with probucol treatment. CONCLUSION: these data suggested that probucol could protect EPCs from ox-LDL through inhibition of ROS production in vivo.