Polycyclic aromatic hydrocarbons induce endothelial injury through miR-155 to promote atherosclerosis.

Polycyclic aromatic hydrocarbons (PAHs) are considered as an external factor that induces atherosclerotic cardiovascular disease. Although miR-155 is known to be involved in cardiovascular disease, whether it is involved in PAH-induced arteriosclerosis remains unclear. We evaluated the effects of PAHs on vascularization, permeability, and miR-155 expression in HUVECs. We found that PAHs-induced sclerosis of HUVECs was characterized by increasing permeability, decreasing proliferation, and vascular lumen number. The expression of miR-155 was upregulated by PAHs treatment, and transfection with miR-155 inhibitor could reverse above effect of PAHs-induced sclerosis. Meanwhile, transcriptome sequencing revealed that 63 genes were downregulated in the group of PAHs treatment alone, and were then upregulated in the miR-155 inhibitor group. These genes were mainly involved in complement and coagulation cascades, cytokine-cytokine receptor interaction, TNF signaling pathway, and NF-kappa B signaling pathway. Among these 63 genes, SERPIND1 was directly targeted and regulated by miR-155. Further in vivo experiments in ApoE-/- mice confirmed that PAH accelerates the development of arteriosclerosis by promoting the expression of miR-155 to downregulate the SERPIND1. Therefore, PAH exaggerates atherosclerosis by activating miR-155-dependent endothelial injury. This study provides a fundamental insight on the miR-155 mechanism for PAHs enhancing atherosclerosis and miR-155 potentially serving as a novel drug target.

Identification of Candidate Genes and MicroRNAs for Acute Myocardial Infarction by Weighted Gene Coexpression Network Analysis.

BACKGROUND: Identification of potential molecular targets of acute myocardial infarction is crucial to our comprehensive understanding of the disease mechanism. However, studies of gene coexpression analysis via jointing multiple microarray data of acute myocardial infarction still remain restricted. METHODS: Microarray data of acute myocardial infarction (GSE48060, GSE66360, GSE97320, and GSE19339) were downloaded from Gene Expression Omnibus database. Three data sets without heterogeneity (GSE48060, GSE66360, and GSE97320) were subjected to differential expression analysis using MetaDE package. Differentially expressed genes having upper 25% variation across samples were imported in weighted gene coexpression network analysis. Functional and pathway enrichment analyses were conducted for genes in the most significant module using DAVID. The predicted microRNAs to regulate target genes in the most significant module were identified using TargetScan. Moreover, subpathway analyses using iSubpathwayMiner package and GenCLiP 2.0 were performed on hub genes with high connective weight in the most significant module. RESULTS: A total of 1027 differentially expressed genes and 33 specific modules were screened out between acute myocardial infarction patients and control samples. Ficolin (collagen/fibrinogen domain containing) 1 (FCN1), CD14 molecule (CD14), S100 calcium binding protein A9 (S100A9), and mitochondrial aldehyde dehydrogenase 2 (ALDH2) were identified as critical target molecules; hsa-let-7d, hsa-let-7b, hsa-miR-124-3, and hsa-miR-9-1 were identified as potential regulators of the expression of the key genes in the two biggest modules. CONCLUSIONS: FCN1, CD14, S100A9, ALDH2, hsa-let-7d, hsa-let-7b, hsa-miR-124-3, and hsa-miR-9-1 were identified as potential candidate regulators in acute myocardial infarction. These findings might provide new comprehension into the underlying molecular mechanism of disease.

Impact of meteorological conditions and PM2.5 on the onset of acute aortic dissection in monsoonal climate.

OBJECTIVE: To investigate the impact of meteorological conditions and PM2.5 on the onset of acute aortic dissection in monsoonal climate. METHODS: A linear regression analysis was performed in monsoonal climate epidemiological survey for a period of four years on the impact of meteorological factors (minimal temperature, mean temperature, maximal temperature, average daily surface temperature, day temperature range, relative humidity, mean wind speed, and atmospheric pressure) and PM2.5 concentration on the daily incidences of acute aortic dissections. Meteorological variables and PM2.5 concentration were retrieved on a daily basis from Beijing Regional Climate Center and the Ministry of Environmental Protection of the People's Republic of China's website, and the daily incidences of acute aortic dissections were retrieved from the Clinical Data Analysis and Reporting System in the Emergency and Critical Care Center of Beijing Anzhen Hospital. RESULTS: During the study period (from January 2011 to December 2014), 1164 patients were identified as having acute aortic dissections. The corresponding incidences in spring and autumn were 0.96 and 1.00, respectively, which significantly higher than that in summer and winter. The incidences of acute aortic dissection in a day could be predicted by diurnal temperature range (DTR) using the following linear multiple regression models: incidences of acute aortic dissection = 0.543 + 0.025 × DTR. CONCLUSION: This is the first study to show an attributable effect of DTR on acute aortic events in monsoonal climate. Our study confirms that meteorological variables were important factors influencing the incidence of acute aortic dissection.

A modified HEART risk score in chest pain patients with suspected non-ST-segment elevation acute coronary syndrome.

OBJECTIVE: To validate a modified HEART [History, Electrocardiograph (ECG), Age, Risk factors and Troponin] risk score in chest pain patients with suspected non-ST-segment elevation acute coronary syndrome (NSTE-ACS) in the emergency department (ED). METHODS: This retrospective cohort study used a prospectively acquired database and chest pain patients admitted to the emergency department with suspected NSTE-ACS were enrolled. Data recorded on arrival at the ED were used. The serum sample of high-sensitivity cardiac Troponin I other than conventional cardiac Troponin I used in the HEART risk score was tested. The modified HEART risk score was calculated. The end point was the occurrence of major adverse cardiac events (MACE) defined as a composite of acute myocardial infarction (AMI), percutaneous intervention (PCI), coronary artery bypass graft (CABG), or all-cause death, within three months after initial presentation. RESULTS: A total of 1,300 patients were enrolled. A total of 606 patients (46.6%) had a MACE within three months: 205 patients (15.8%) were diagnosed with AMI, 465 patients (35.8%) underwent PCI, and 119 patients (9.2%) underwent CABG. There were 10 (0.8%) deaths. A progressive, significant pattern of increasing event rate was observed as the score increased (P < 0.001 by χ (2) for trend). The area under the receiver operating characteristic curve was 0.84. All patients were classified into three groups: low risk (score 0-2), intermediate risk (score 3-4), and high risk (score 5-10). Event rates were 1.1%, 18.5%, and 67.0%, respectively (P < 0.001). CONCLUSIONS: The modified HEART risk score was validated in chest pain patients with suspected NSTE-ACS and may complement MACE risk assessment and patients triage in the ED. A prospective study of the score is warranted.

Impact of the origin of sinus node artery on recurrence after pulmonary vein isolation in patients with paroxysmal atrial fibrillation.

BACKGROUND: Major atrial coronary arteries, including the sinus node artery (SNA), were commonly found in the areas involved in atrial fibrillation (AF) ablation and could cause difficulties in achieving linear block at the left atrial (LA) roof. The SNA is a major atrial coronary artery of the atrial coronary circulation. This study aimed to determine impact of the origin of SNA on recurrence of AF after pulmonary vein isolation (PVI) in patients with paroxysmal AF. METHODS: Seventy-eight patients underwent coronary angiography for suspected coronary heart disease, followed by catheter ablation for paroxysmal AF. According to the origin of SNA from angiographic findings, they were divided into right SNA group (SNA originating from the right coronary artery) and left SNA group (SNA originating from the left circumflex artery). Guided by an electroanatomic mapping system, circumferential pulmonary vein ablation (CPVA) was performed in both groups and PVI was the procedural endpoint. All patients were followed up at 1, 3, 6, 9 and 12 months post-ablation. Recurrence was defined as any episode of atrial tachyarrhythmias (ATAs), including AF, atrial flutter or atrial tachycardia, that lasted longer than 30 seconds after a blanking period of 3 months. RESULTS: The SNA originated from the right coronary artery in 34 patients (43.6%) and the left circumflex artery in 44 patients (56.4%). Freedom from AF and antiarrhythmic drugs (AADs) at 1 year was 67.9% (53/78) for all patients. After 1 year follow-up, 79.4% (27/34) in right SNA group and 59.1% (26/44) in left SNA group (P = 0.042) were in sinus rhythm. On multivariate analysis, left atrium size (HR = 1.451, 95%CI: 1.240 - 1.697, P < 0.001) and a left SNA (HR = 6.22, 95%CI: 2.01 - 19.25, P = 0.002) were the independent predictors of AF recurrence. CONCLUSIONS: The left SNA is more frequent in the patients with paroxysmal AF. After one year follow-up, the presence of a left SNA was identified as an independent predictor of AF recurrence after CPVA in paroxysmal AF.

Outcome of catheter ablation of atrial fibrillation in patients with prior ischemic stroke.

BACKGROUND: Catheter ablation for atrial fibrillation (AF) has been demonstrated to be effective in a subsets of patients with AF. However, very few data are available in regard to patients with prior history of stroke undergoing catheter ablation. This study aimed to investigate the outcome of catheter ablation in AF patients with prior ischemic stroke. METHODS: Between January 2008 and December 2011, of 1897 consecutive patients who presented at Beijing An Zhen Hospital for treatment of drug-refractory AF, 172 (9.1%) patients in the study population had a history of ischemic stroke. All patients underwent catheter ablation and were followed up to assess maintenance of sinus rhythm and recurrence of symptomatic stroke. RESULTS: Among these 1897 patients, 1768 (93.2%) who had complete follow-up information for a minimum of six months were included in the final analysis. Patients in the stroke group (group I) and the no-stroke group (group II) were similar in regards to gender, body mass index (BMI), history of diabetes, type of AF, and left atrial size. The patients in group I were older than those in group II, and had a higher incidence of hypertension, chronic heart failure, lower left ventricular ejection fraction (LVEF), and higher CHADS2 scores. Six months after ablation, 107 (68.6%) patients in group I and 1403 (87.1%) in group II had discontinued warfarin treatment (P < 0.001). During a median follow-up of (633 ± 415) days, 65 patients in the group I and 638 in group II experienced AF recurrence, and five patients in group I and 28 in group II developed symptomatic stroke. The rates of AF recurrence and recurrent stroke were similar between group I and group II (41.7% vs. 39.6%, P = 0.611; 3.2% vs. 1.7%, P = 0.219; respectively). CONCLUSION: Catheter ablation of AF in patients with prior stroke is feasible and efficient.

Serum uric acid levels correlate with recurrence of paroxysmal atrial fibrillation after catheter ablation.

BACKGROUND: Recently there has been a great deal of interest in the role of serum uric acid (SUA) in atrial fibrillation (AF). The objective of this study was to establish whether there is a relationship between levels of SUA and recurrence of paroxysmal AF after catheter ablation. METHODS: Three hundred and thirty patients diagnosed with paroxysmal AF were analyzed. Patients were categorized into quartiles on the basis of their pre-operative SUA measurement and follow-up, and Kaplan-Meier estimation with a Log-rank test was used for the analysis of the influence of SUA on the recurrence of AF. Pre-procedural clinical variables were correlated with the clinical outcome after ablation using multivariate Logistic analysis. A Cox proportional hazards model was used to estimate the relationship between SUA and the recurrence of AF. RESULTS: After a mean follow-up of (9.341 ± 3.667) (range 3.0 - 16.3) months, recurrence rates from the lowest SUA quartile to the highest SUA quartile were 16.0%, 26.4%, 28.3%, and 29.3% respectively (P = 0.014). After adjustment for gender, body mass index (BMI), hypertension, serum levels of high sensitivity C-reactive protein (hsCRP), triglyceride (TG), left atrial diameter (LA), estimated glomerular filtration rate (eGFR), and SUA, there was an increased risk of recurrence in subjects in the highest SUA quartile compared with those in the lowest quartile (hazard ratio 2.804, 95% confidence interval 1.466 - 5.362, P = 0.002). Following multivariate Logistical analysis, SUA was found to be an independent predictor of recurrence (hazard ratio 1.613, 95% confidence interval 1.601 - 1.625, P = 0.014). CONCLUSION: In a retrospective study of patients with paroxysmal AF undergoing catheter ablation, elevated preoperative SUA levels were associated with a higher rate of recurrence of AF.