3, 4-Benzopyrene (Bap) aggravated abdominal aortic aneurysm formation by targeting pyroptosis in smooth muscle cells through ET-1 mediated NLRP3-inflammasome activation.

According to epidemiological studies, smoking is one of the leading causes of the high incidence of abdominal aortic aneurysms (AAA).3,4-Benzopyrene (Bap) is a by-product of coal tar and tobacco combustion produced by the incomplete combustion of organic fuels. It is an essential component of both automobile exhaust and tobacco smoke, it is also an important member of the air pollutants. However, the exact mechanism by which Bap can worsen the condition of patients with AAA and increase the mortality of patients with AAA remains unknown. This research aims to investigate the role of Bap in inducing pyroptosis in AAA. In vitro experiments, we revealed that pyroptosis-Gasdermin D (GSDMD) increased when Bap was used. Additionally, the release of inflammatory factors, such as IL-1ß and IL-18 were also rising. An mRNA sequencing analysis revealed that macrophages expressed a high level of the endothelin gene when cells were stimulated by Bap. It seemed that smooth muscle cells pyroptosis was related to macrophages. Experiments revealed that endothelin could increase the calcium ion concentration in smooth muscle cells, resulting in a large amount of ROS and activation of NLRP3 inflammasomes. We discovered that treatment with endothelin receptor antagonist (ABT-546) in vivo and calcium ion chelator (BAPTA) in vitro decreased AAA diameter, downregulated NLRP3 inflammasomes and ROS, and significantly reduced the number of activated GSDMD. Inflammatory mediators were released at a lower level. These findings suggest that Bap-induced pyroptosis may be mediated by the ET-1-Ca2+-inflammasome pathway, providing a new way to reduce mortality in AAA patients.

The Neutrophil-to-Albumin Ratio as a New Predictor of All-Cause Mortality in Patients with Heart Failure.

BACKGROUND: Neutrophils and albumin had been shown to be independent predictors of mortality from various diseases. Purpose of this study was to investigate the effect of neutrophil-to-albumin ratio (NPAR) as an independent predictor of mortality in heart failure (HF) patients. METHODS: Data were extracted from Medical Information Mart for Intensive Care-III database. Primary outcome was 30-day mortality, secondary outcomes were in-hospital, 90-day, 365-day mortality, length of stay (LOS) in hospital. Cox proportional hazards regression model and receiver operating characteristic (ROC) curve analysis and Pearson correlation analysis were used. RESULTS: The HR (95% CI) values of the mid-tertile and the upper tertile were 1.27 (1.01 to 1.59) and 2.29 (1.87 to 2.81) in 30-day mortality compared with the reference. The trend continued after adjusted for demographic and clinical variables. In the secondary outcomes were the same trends. The data of the Second Affiliated Hospital of Wenzhou Medical University showed the correlation coefficient between hospital LOS with NPAR. CONCLUSION: NPAR was an independent factor of mortality in HF patients, which was correlated with hospital LOS. Our results need to be verified by prospective studies.

Low-Density Lipoprotein Cholesterol is Inversely Associated with All-Cause Mortality of Patients in the Coronary Care Unit.

OBJECTIVE: The aims of this study were to investigate the relationship between low-density lipoprotein cholesterol (LDL-C) levels and all-cause mortality in coronary care unit (CCU) patients, adjusting for a wide range of potential confounding factors, to examine the potential of LDL-C in predicting the prognostic value of CCU patients. METHODS: Clinical data were extracted from Medical Information Mart for Intensive Care-III database (MIMIC-III database version v.1.4). Baseline data were collected within 24 hours after the patient was first admitted to the hospital. The primary endpoint of our study is 30-day all-cause mortality. The secondary endpoints are 90-day and one-year all-cause mortality and infections. Cox proportional hazard regression and propensity score-matched (PSM) analysis were used to analyze the association between LDL-C levels and prognostic value of CCU patients. RESULTS: We included a total of 1476 patients with an average age of 66.7 ± 14.1 years (66% male). For 30-day all-cause mortality, the hazard ratio (95% confidence interval) of high LDL-C level group (≥ 55 mg/dl) was 0.42 (0.29, 0.62), which was compared with low LDL-C level group (< 55 mg/dl) in unadjusted model. After adjusting for age, gender and race, the association still existed (P < 0.05), and the HR (95% CI) was 0.49 (0.33, 0.72). Further adjustment of possible covariates showed similar correlation (P < 0.05), and HR (95% CI) was 0.65 (0.43, 0.97). Similar correlations were observed for 90-day and one-year all-cause mortality. The relationship between all-cause mortality and LDL-C levels in CCU patients was further verified by propensity score-matched (PSM) analysis. In addition, the higher the LDL-C level, the lower the risk of infection, odds ratio (OR) values in the three models were less than 1 (P < 0.05). CONCLUSION: Our data suggest that high LDL-C level is associated with a reduced risk of 30-day, 90-day, and one-year mortality of patients in the CCU. And this result is still stable in the PSM model. The results need to be verified in prospective trials.

The safety of catheter ablation for premature ventricular contractions in patients without structural heart disease.

BACKGROUND: Patients with frequent premature ventricular contractions (PVCs) are often symptomatic. Catheter ablation was usually indicated to eliminate symptoms in patients with PVCs-induced cardiomyopathy. Currently, PVCs-ablation is also applied for patients with PVCs and no structural heart diseases (SHD); however, the safety and efficacy of ablation in these patients remains unclear. METHODS: In this retrospective study, data from patients who underwent ablation for PVCs from January 2010 to December 2016 at our hospital was retrieved. Predictors of complications and acute procedural success were evaluated. RESULTS: A total of 1231 patients (mean age 47.8 ± 16.8 years, 59% female) were included. The overall complication rate was 2.7%, and the most common complication was hydropericardium. Two ablation-related mortalities occurred. One patient died of coronary artery injury during the procedure and the other died from infectious endocarditis. Location (left ventricle and epicardium) was the main predictor of complications, with right ventricular outflow tract (RVOT) predicting fewer complications. The acute procedural success rate was 94.1% in all patients. The main predictor of acute procedural success was RVOT origin, while an epicardial origin was a predictor of procedural failure. CONCLUSION: Locations of left ventricle and epicardium were predictors of procedural complications for patients with PVCs. Therefore, ablation is not recommended in these patients. For other origins of PVCs, particularly RVOT origin, ablation is a safety and effective treatment.

Common and distinctive electrocardiographic characteristics and effective catheter ablation of idiopathic ventricular arrhythmias originating from different areas of ventricular septum adjacent to atrioventricular annulus.

OBJECTIVE: To investigate electrocardiographic (ECG) characteristics and radiofrequency catheter ablation (RFCA) efficacy for premature ventricular complexes (PVCs) and idiopathic ventricular tachycardias (IVTs) originating from ventricular septum areas adjacent to atrioventricular annulus (VS-AVA). METHODS: Among 1,505 consecutive PVCs/IVTs cases, 106 (7.04%) were confirmed as origin of VS-AVA guided by both fluoroscopy and three-dimensional mapping system during RFCA. Characteristics of surface 12-lead ECG were analyzed. RESULTS: The overall success rate for RFCA of PVCs/IVTs originating from VS-AVA was 82.08% (87/106), common ECG characteristics were: mainly positive R wave on lead I; dominant-positive R on aVL (91/106, 85.85%) for most, r (1/106, 0.94%) or qr (14/106, 13.21%) in few; QS or qs on aVR; and decreasing R wave amplitude and increasing S wave depth on II, III, and aVF from superior to inferior septum; and S wave on at least one inferior lead (generally III). Distinctive ECG features were: precordial transition zone before or after V2 for septum adjacent to mitral (MA, 19/19, 100.0%) or tricuspid (TA, 74/87,85.05%) annulus origin; initial r wave and rS on V1 for superior septum near TA (above His bundle) origin (9/10, 90.0%) with no initial r wave for most other origins; and QS on V1 for mid-inferior septum near TA origin (73/77, 94.81%) and QR (Qr, qR or qr) on V1 for septum near MA origin (17/19, 89.47%). CONCLUSION: Distinctive ECG characteristics of PVCs/IVTs originating from VS-AVA aid in origin localization guiding effective RFCA.

The protective effect of astragaloside IV against benzo[a]pyrene induced endothelial progenitor cell dysfunction.

AIMS: Benzo[a]pyrene (BaP), a prominent component of tobacco, has been revealed to induce damage to endothelial progenitor cells (EPCs). Astragaloside IV (AS-IV) is widely used for the treatment of cardiovascular diseases in China. In this study, we evaluated the effects of AS-IV on the function of human EPCs after BaP exposure and explored the underlying mechanism. MATERIALS AND METHODS: Human umbilical cord blood mononuclear cells were isolated using density gradient centrifugation. Cells of the 4th passage were randomly divided into 6 groups. EPCs of experimental groups were pre-treated with different concentrations (2, 10 and 50 µg/mL) of AS-IV for 2h before exposure to BaP (20 µM) for 24h. The proliferation, migration, and adhesion of the treated EPCs were evaluated using a cell counting kit-8, Transwell assay and adhesion assay respectively. Interleukin-1ß, tumor necrosis factor-α, malondialdehyde and SOD contents in the supernatant were evaluated. The expression of RAGE protein was measured by Western blotting. KEY FINDINGS: The results demonstrated that AS-IV pre-treatment significantly improved BaP-induced dysfunction of EPCs in terms of proliferation, migration and adhesion. Furthermore, AS-IV reduced the production of reactive oxygen species, malondialdehyde, interleukin-1ß and tumor necrosis factor-α of the BaP-treated EPCs. Finally AS-IV pre-treated EPCs showed an increased SOD activity and decreased RAGE protein expression. SIGNIFICANCE: AS-IV is able to prevent BaP-mediated EPC dysfunction by at least inhibiting oxidative stress through the RAGE pathway.

Ox-LDL induces dysfunction of endothelial progenitor cells via activation of NF-κB.

Dyslipidemia increases the risks for atherosclerosis in part by impairing endothelial integrity. Endothelial progenitor cells (EPCs) are thought to contribute to endothelial recovery after arterial injury. Oxidized low-density lipoprotein (ox-LDL) can induce EPC dysfunction, but the underlying mechanism is not well understood. Human EPCs were cultured in endothelial growth medium supplemented with VEGF (10 ng/mL) and bFGF (10 ng/mL). The cells were treated with ox-LDL (50 µg/mL). EPC proliferation was assayed by using CCK8 kits. Expression and translocation of nuclear factor-kabba B (NF-κB) were evaluated. The level of reactive oxygen species (ROS) in cells was measured using H2DCF-DA as a fluorescence probe. The activity of NADPH oxidase activity was determined by colorimetric assay. Ox-LDL significantly decreased the proliferation, migration, and adhesion capacity of EPCs, while significantly increased ROS production and NADPH oxidase expression. Ox-LDL induced NF-κB P65 mRNA expression and translocation in EPCs. Thus ox-LDL can induce EPC dysfunction at least by increasing expression and translocation of NF-κB P65 and NADPH oxidase activity, which represents a new mechanism of lipidemia-induced vascular injury.

Electrocardiogram features of premature ventricular contractions/ventricular tachycardia originating from the left ventricular outflow tract and the treatment outcome of radiofrequency catheter ablation.

BACKGROUND: Radiofrequency catheter ablation (RFCA) has been used for the ablation of premature ventricular contractions (PVCs) or ventricular tachycardia (VT). To date, the mapping and catheter ablation of the arrhythmias originating from the left ventricular outflow tract (LVOT) has not been specified. This study investigates the electrocardiogram (ECG) feature of PVCs or VT originating from the LVOT. Moreover, the treatment outcome of RFCA is analyzed. METHODS: Mapping and ablation were performed on the supravalvular or subvalvular aorta in 52 cases with PVCs/VT originating from the LVOT. The data were compared with those from 104 patients with PVCs/VT originating from the right ventricular outflow tract (RVOT). A differential procedure was prepared based on the comparison of the ECG features of PVCs/VT originating from the RVOT, LVOT, and their different parts. RESULTS: Among 52 cases with PVCs originating from the LVOT, 47 were successfully treated by RFCA, with a success rate of 90.38%. Several differences among the 12-lead ECG features were observed from the RVOT and LVOT in the left and right coronary sinus groups, as well as under the left coronary sinus group (left fibrous trigone): (1) If the precordial leads transition 0 are considered as the diagnostic parameters of PVCs/VT originating from the LVOT, then the sensitivity, specificity, as well as positive and negative predictive values are 94.12%, 93.00%, 87.27%, and 96.88%, respectively; (2) The analysis of different subgroups of the LVOT are as follows: (a) A mainly positive wave of r or m pattern was recorded in the lead I in 72.73% of patients in the right coronary sinus group, versus 12.90% of patients in the left coronary sinus group, and 0% in the under left coronary sinus group. (b) All patients in the right coronary sinus group presented waves of RII>RIII and QSaVR>QSaVL, whereas most patients in the other two groups showed waves of RIII>RII and QSaVL>QSaVR. (c) Most patients in the under left coronary sinus group in lead V1 had a mainly positive wave (R) (77.78%), whereas those in the right (81.82%) and left (62.50%) coronary sinus groups had mainly negative waves (rS). CONCLUSIONS: RFCA is a safe and effective curative therapy for PVCs/VT originating from the LVOT. The 12-lead ECG features of the LVOT from different origins exhibit certain distinctions.