Attenuation of atrial remodeling by aliskiren via affecting oxidative stress, inflammation and PI3K/Akt signaling pathway.

INTRODUCTION: Atrial fibrillation (AF) is the most common type of arrhythmia. Atrial remodeling is a major factor to the AF substrate. The purpose of the study is to explore whether aliskiren (ALS) has a cardioprotective effect and its potential molecular mechanisms on atrial remodeling. METHODS: In acute experiments, dogs were randomly assigned to Sham, Paced and Paced+aliskiren (10 mg kg-1) (Paced+ALS) groups, with 7 dogs in each group. Rapid atrial pacing (RAP) was maintained at 600 bpm for 2 h for paced and Paced+ALS groups and atrial effective refractory periods (AERPs), inducibility of AF (AFi) and average duration time (ADT) were measured. In chronic experiments, there were 5 groups: Sham, Sham+ALS, Paced, Paced+ALS and Paced+ALS+PI3K antagonist wortmannin (WM) (70 µg kg-1 day-1). RAP at 500 beats/min was maintained for 2 weeks. Inflammation and oxidative stress indicators were measured by ELISA assay, echocardiogram and pathology were used to assess atrial structural remodeling, phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/Akt) signaling pathways were studied by RT-PCR and western blotting to evaluate whether the cardioprotective effect of ALS works through PI3K/Akt signaling pathway. RESULTS: The electrophysiological changes were observed after 2-h pacing. The AERP shortened with increased AFi and ADT, which was attenuated by ALS (P < 0.05). After pacing for 2 weeks, oxidative stress and inflammation markers in the Paced group were significantly higher than those in the Sham group (P < 0.01) and were reduced by ALS treatment (P < 0.01). The reduced level of antioxidant enzymes caused by RAP was also found to be elevated in ALS-treated group (P < 0.01). The results of pathology and echocardiography showed that RAP can cause atrial enlargement, fibrosis (P < 0.01), and were attenuated in ALS treatment group. The PI3K/Akt signaling pathway were downregulated induced by RAP. ALS could upregulate the PI3K/Akt pathway expression (P < 0.05). Furthermore, the cardioprotective effects in structural remodeling of ALS were suppressed by WM. CONCLUSIONS: ALS may offer cardioprotection in RAP-induced atrial remodeling, which may partly be ascribed to its anti-inflammatory and anti-oxidative stress action and the regulation of PI3K/Akt signaling pathway.

Serum Beta-2 Microglobulin: A Possible Biomarker for Atrial Fibrillation.

BACKGROUND Atrial fibrillation (AF) is the most common persistent arrhythmia that can cause complications (including stroke). Therefore, its diagnosis and treatment require increased attention. Although beta-2 microglobulin (b2-MG) is a novel marker of cardiovascular disease, its role in AF has not been evaluated. MATERIAL AND METHODS We conducted a case-control study with 61 patients who had normal heart rhythm (control group) and 60 patients with AF (research group). We analyzed the serum b2-MG levels in both groups and performed multivariate analysis to assess the correlation between b2-MG and left atrial remodeling. In addition, b2-MG levels were compared between the left atrial blood and peripheral venous blood of another set of 57 patients with AF, who underwent cryoballoon ablation. RESULTS There were no statistically significant differences in the baseline characteristics (age, sex, history of hypertension, diabetes mellitus, previous stroke, coronary heart disease, and estimated glomerular filtration rate) of the control and research groups. The left atrial anteroposterior diameters (LAD) and left ventricular end-systolic diameters in the AF group were significantly larger compared to the control group (P<0.01). Serum ß2-MG levels in patients with AF were significantly higher (P<0.01) and positively correlated with the LAD (B-coefficient 25.482, 95% CI 14.410~36.554, P<0.01), serum ß2-MG levels in the left atrial blood were significantly higher than those in peripheral venous blood (P<0.01), and serum ß2-MG levels were an independent predictor of AF. CONCLUSIONS With the development of atrial fibrillation, the serum ß2-MG levels increase and are closely related to the left atrial remodeling due to AF. Therefore, ß2-MG can be an effective biomarker for predicting AF.

Excessive Supraventricular Ectopic Activity and Adverse Cardiovascular Outcomes: a Systematic Review and Meta-analysis.

PURPOSE OF REVIEW: Excessive supraventricular ectopic activity (ESVEA), in the form of frequent premature atrial contractions (PACs) and runs of PACs, is commonly observed in clinical practice and is frequently considered to be benign. Yet, recent studies have demonstrated a link between ESVEA and adverse cardiovascular outcomes. The aim of this meta-analysis was to examine the association between ESVEA and the risk of atrial fibrillation (AF), stroke, and mortality. RECENT FINDINGS: A systematic search was performed in PubMed, EMBASE, and the Cochrane Library up to December 2017 to identify studies assessing adverse cardiovascular outcomes in patients with ESVEA, recorded on ambulatory electrocardiography. ESVEA was defined as a burden of PACs > 30 PACs/h or any runs of ≥20 PACs. The risk estimates for EVSEA and each clinical endpoint were pooled and analyzed separately. RESULTS: Five studies comprising 7545 participants were included in this meta-analysis. The pooled analysis showed that ESVEA doubled the risk of AF (HR 2.19, 95% CI 1.70-2.82). ESVEA was also associated with a higher incidence of stroke (HR 2.23, 95% CI 1.24-4.02). Finally, ESVEA was associated with higher all-cause mortality (HR 1.61, 95% CI 1.25-2.07). Our meta-analysis found that ESVEA is closely associated with AF, stroke, and all-cause mortality. Further studies are required to examine the implication of therapeutic strategies in patients with ESVEA, in order to prevent potential subsequent adverse cardiovascular outcomes.

Suppression of experimental atrial fibrillation in a canine model of rapid atrial pacing by the phosphodiesterase 3 inhibitor cilostazol.

OBJECTIVE: Atrial fibrillation (AF) represents the most common arrhythmia encountered in cardiology department. The purpose of this study was designed to investigate whether cilostazol, an oral phosphodiesterase 3 inhibitor (PDE3) could have protective effects on atrial remodeling in a canine model of AF and explore the potential molecular mechanisms. METHODS: Dogs were randomly assigned to Sham, Paced, Paced + cilostazol group, 7 dogs in each group. In Sham group, pacemaker was instrumented but without pacing. Rapid atrial pacing (RAP) at 600 or 500 bpm/min was maintained in Paced group and Paced + cilo group for 2 h or 2 weeks in acute or chronic experiment, respectively. The Paced + cilo group of dogs were pretreated with cilostazol orally (10 mg·kg-1·d-1, cilo) for 1 h or 2 days prior RAP induction and served as treatment group. Atrial effective refractory periods (AERP) at different basic cycle lengths (BCLs), inducibility, and duration time of AF were measured after pacing for 2 h. The blood sample, echocardiography, histopathology, inflammation and oxidative stress makers, protein and mRNA expression levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 were detected after 2 weeks pacing in each group. RESULTS: Significant changes in electrophysiological parameters were observed in the acute RAP canine model, the AERPs shortened with increased inducibility and duration of AF, which was attenuated by cilostazol (P < 0.05). The serum inflammation makers as interleukin-8 (IL-8) and toll like receptor 4 (TLR 4) levels and oxidative stress indicators like xanthine oxidative (XO) and reactive oxygen species (ROS) in the Paced group was significantly higher than that in Sham group (P < 0.01), and was significantly reduced by cilostazol treatment (P < 0.01). The level of mean platelet volume (MPV) which is one of the platelet indices was significantly elevated in Paced group (P < 0.01). While after cilostazol treated for 2 weeks, the level of MPV was obviously decreased than Paced group (P < 0.01). Pathology and echocardiography studies showed that cilostazol can also prevent RAP induced cardiac fibrosis and structural remodeling. The MPV level has close correlations with IL-8, TLR4, XO and ROS (all P < 0.01). MMP-2 and MMP-9 expression were significantly increased in Paced group (all P < 0.01), which can be attenuated by cilostazol. CONCLUSIONS: Cilostazol may have protective effects on RAP-induced atrial remodeling by anti-inflammatory, anti-oxidative stress action and regulate the extracellular collagen matrix in a canine model. Moreover, MPV level is associated with inflammation and oxidative stress response of RAP, which might be an important predictors of new-onset and recurrent AF.

Discrete potentials guided radiofrequency ablation for idiopathic outflow tract ventricular arrhythmias.

AIMS: Discrete potentials (DPs) have been recorded and targeted as the site of ablation of the outflow tract arrhythmias. The aim of the present study was to investigate the significance of DPs with respect to mapping and ablation for idiopathic outflow tract premature ventricular contractions (PVCs) or ventricular tachycardias (VTs). METHODS AND RESULTS: Seventeen consecutive patients with idiopathic right or left ventricular outflow tract PVCs/VTs who underwent radiofrequency catheter ablation were included. Intracardiac electrograms during the mapping and ablation were analysed. During sinus rhythm, sharp high-frequency DPs that displayed double or multiple components were recorded following or buried in the local ventricular electrograms in all of the 17 patients, peak amplitude 0.51 ± 0.21 mV. The same potential was recorded prior to the local ventricular potential of the PVCs/VTs. Spontaneous reversal of the relationship of the DPs to the local ventricular electrogram during the arrhythmias was noted. The DPs were related to a region of low voltage showed by intracardiac high-density contact mapping. At the sites with DPs, lower unipolar and bipolar ventricular voltage of sinus beats were noted compared with the adjacent regions without DPs (unipolar: 6.1 ± 1.8 vs. 8.3 ± 2.3 mV, P < 0.05; bipolar: 0.62 ± 0.45 vs. 1.03 ± 0.60 mV, P < 0.05). The targeted DPs were still present in 12 patients after successful elimination of the ectopies. Discrete potentials were not present in seven controls. CONCLUSION: Discrete potentials and related low-voltage regions were common in idiopathic outflow tract ventricular arrhythmias. Discrete potential- and substrate-guided ablation strategy will help to reduce the recurrence of idiopathic outflow tract arrhythmias.

Radiofrequency catheter ablation at the non-coronary cusp for the treatment of para-hisian accessory pathways.

AIMS: Radiofrequency catheter ablation (RFCA) is well established as a definitive therapy of accessory pathways (APs). Successful RFCA of anteroseptal APs at the non-coronary cusp (NCC) have been reported in several case reports. We aimed to evaluate the prevalence, safety, efficacy, and long-term outcome of RFCA at the NCC for the treatment of para-hisian APs. METHODS AND RESULTS: Our study included 17 patients (58.8% female, mean age 46.9 ± 15.9 years) with para-hisian APs. We performed two different ablation approaches which targeted at either the right anterior septum (RAS) (n = 10) or the NCC (n = 7) as the initial target. We compared safety, efficacy, and long-term outcome between these two approaches. The para-hisian APs were successfully ablated in 15 patients and damaged in 1 patient, for the remaining patients, the ablation was abandoned for the suspicion of no atrioventricular conduction. Considering all ablation sites of the para-hisian APs, radiofrequency (RF) delivered at the NCC had a higher success rate (11/12 vs. 5/12, P < 0.05) and a lower complication rate (0/12 vs. 4/12, P < 0.05) compared with the RAS. During a mean follow-up period of 22.4 ± 15.0 months, all the patients were free of arrhythmias without any anti-arrhythmic drugs. CONCLUSION: Para-hisian APs can be safely and effectively ablated at the NCC. Compared with the ablation at the RAS, RF delivered at the NCC has a higher immediate success, lower complication rate, and good long-term outcome.

Protective effects of aliskiren on atrial ionic remodeling in a canine model of rapid atrial pacing.

PURPOSE: Aliskiren inhibits the activation of the renin-angiotensin system. Here, we investigated the effects of aliskiren on chronic atrial iron remodeling in the experimental canine model of rapid atrial pacing. METHODS: Twenty-eight dogs were assigned to sham (S), control paced (C), paced + aliskiren (10 mg Kg(-1) d(-1), A1), and paced + aliskiren (20 mg Kg(-1) d(-1), A2) groups. Rapid atrial pacing at 500 bpm was maintained for 2 weeks, while group S was not paced. Levels of serum angiotensin-converting enzyme and angiotensin II after pacing were determined by ELISA. Whole-cell patch-clamp technique, western blot, and RT-PCR were applied to assess atrial ionic remodeling. RESULTS: The density of I CaL and I Na currents (pA/pF) was significantly lower in group C compared with group S (I CaL: -4.09 ± 1.46 vs. -6.12 ± 0.58,P < 0.05; I Na: 30.48 ± 6.08 vs. 46.31 ± 4.73, P < 0.05). However, the high dose of aliskiren elevated the density of I CaL and I Na currents compared with group C (I CaL: -6.23 ± 1.35 vs. -4.09 ± 1.46, P < 0.05; I Na: 58.62 ± 16.17 vs. 30.48 ± 6.08, P < 0.01). The relative mRNA and protein expression levels of Cav1.2 and Nav1.5α were downregulated in group C respectively (Cav1.2: 0.46 ± 0.08; Nav1.5α: 0.52 ± 0.08, P < 0.01; Cav1.2: 0.31 ± 0.03; Nav1.5α: 0.41 ± 0.04, P < 0.01;), but were upregulated by aliskiren. CONCLUSIONS: Aliskiren has protective effects on atrial tachycardia-induced atrial ionic remodeling.

Bioinspired Mechanically Robust and Recyclable Hydrogel Microfibers Based on Hydrogen-Bond Nanoclusters.

Mechanically robust hydrogel fibers have demonstrated great potential in energy dissipation and shock-absorbing applications. However, developing such materials that are recyclable, energy-efficient, and environmentally friendly remains an enormous challenge. Herein, inspired by spider silk, a continuous and scalable method is introduced for spinning a polyacrylamide hydrogel microfiber with a hierarchical sheath-core structure under ambient conditions. Applying pre-stretch and twist in the as-spun hydrogel microfibers results in a tensile strength of 525 MPa, a toughness of 385 MJ m-3, and a damping capacity of 99%, which is attributed to the reinforcement of hydrogen-bond nanoclusters within the microfiber matrix. Moreover, it maintains both structural and mechanical stability for several days, and can be directly dissolved in water, providing a sustainable spinning dope for re-spinning into new microfibers. This work provides a new strategy for the spinning of robust and recyclable hydrogel-based fibrous materials.

Establishing superfine nanofibrils for robust polyelectrolyte artificial spider silk and powerful artificial muscles.

Spider silk exhibits an excellent combination of high strength and toughness, which originates from the hierarchical self-assembled structure of spidroin during fiber spinning. In this work, superfine nanofibrils are established in polyelectrolyte artificial spider silk by optimizing the flexibility of polymer chains, which exhibits combination of breaking strength and toughness ranging from 1.83 GPa and 238 MJ m-3 to 0.53 GPa and 700 MJ m-3, respectively. This is achieved by introducing ions to control the dissociation of polymer chains and evaporation-induced self-assembly under external stress. In addition, the artificial spider silk possesses thermally-driven supercontraction ability. This work provides inspiration for the design of high-performance fiber materials.

CircRNA_0263 and circRNA_1507 are dysregulated in a rat model of atrial fibrosis induced by chronic intermittent hypoxia.

Aims: This study aimed to characterize circular RNA (circRNA) profiles associated with atrial fibrosis-related atrial fibrillation (AF) and reveal critical circRNAs for AF. Methods: Sprague Dawley rats were randomly divided into control and atrial fibrosis-related AF groups (n = 15 in each group). The rats in the atrial fibrosis-related AF group were induced by chronic intermittent hypoxia (CIH), and then confirmed by electrocardiograms, echocardiography, hematoxylin-eosin staining, Masson staining, immunohistochemistry assays and western blotting. After that, the atrial tissues were sent for circRNA sequencing, and the differentially expressed circRNAs were identified and validated by quantitative real-time polymerase chain reaction (qRT-PCR). Finally, a series of cell experiments were performed to explore the roles of two crucial circRNAs in rat atrial fibroblasts. Results: A CIH-induced AF model was successfully established in the rats. After sequencing, five upregulated and 11 downregulated circRNAs were identified in the CIH-induced AF group. These dysregulated circRNAs were primarily associated with "carbohydrate metabolism" and "cardiovascular diseases". Two circRNAs (circRNA_0263 and circRNA_1507) were predicted to regulate target gene expression by interacting with corresponding miRNAs, including rno-miR-29b-5p, rno-miR-29b-3p, rno-miR-496-5p, rno-miR-136-5p, and novel123-mature. Additionally, circRNA_0263 knockdown and circRNA_1507 overexpression inhibited the cell viability of fibroblasts, and downregulated the expression of fibrosis-related proteins. Conclusion: A series of circRNAs were identified as dysregulated in an AF rat model, and circRNA_0263 and circRNA_1507 might be crucial for atrial fibrosis-related AF development by competing with several miRNAs.

Effects of radiofrequency balloon angioplasty on the abdominal aorta in atherosclerotic rabbits.

OBJECTIVES: A novel temperature-controlled intravascular radiofrequency balloon angioplasty (RFBA) technique was designed and developed for atherosclerosis (AS) management. METHODS: After establishing an AS model based on a balloon denudation injury of the abdominal aorta and a high cholesterol diet in rabbits, 46 animals were randomly assigned to the RFBA group (n = 28) or the plain balloon angioplasty (PBA) group (n = 28). The groups were further subdivided based on post-treatment euthanasia times (1 hour, 7 days, 14 days, and 28 days). Histopathological changes were observed by hematoxylin and eosin and Masson's staining. Immunohistochemistry, western blotting, and real-time quantitative polymerase chain reaction were used to detect changes in pro-inflammatory, anti-inflammatory, and apoptotic factors; TGF-ß/Smad-2 pathway protein Immune levels; and mRNA levels in tissues, respectively. RESULTS: The vascular lumen area in the RFBA group was larger than that in the PBA group at the same time points, although the change in the vascular lumen area was not different between groups. The expression of Bax, TGF-ß, Smad-2, and Caspase-3 in the RFBA group was significantly higher than that in the PBA group. The expression levels of Bcl-2 in the RFBA group were significantly lower than those in the PBA group. CONCLUSIONS: At 28 days, RFBA dilated the atherosclerotic blood vessels and thickened the fibrous cap of atherosclerotic plaques to promote plaque stability. RFBA was also found to activate apoptotic factors and the TGF-/Smad-2 inflammatory pathway.

Establishment of a lncRNA-miRNA-mRNA network in a rat model of atrial fibrosis by whole transcriptome sequencing.

PURPOSE: Dysregulation of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) plays important roles in atrial fibrillation (AF). This study aimed to identify crucial lncRNAs, miRNAs, and mRNAs in AF based on whole transcriptome sequencing. METHODS: Thirty Sprague Dawley rats were randomly stratified into control and chronic intermittent hypoxia (CIH) groups (n = 15 in each). Hematoxylin-eosin staining, Masson staining, immunohistochemical assay, and western blotting were used to evaluate this model. Thereafter, atrial tissues were sent for whole transcriptome sequencing. Finally, fibrosis-related competing endogenous RNA (ceRNA) regulatory networks were built, and the relative levels of lncRNAs, miRNAs, and mRNAs were validated by real-time quantitative polymerase chain reaction (RT-qPCR) or western blotting. RESULTS: A CIH-induced atrial fibrosis rat model was successfully constructed. After sequencing, 268 differentially expressed lncRNAs (DELs), 20 differentially expressed miRNAs (DEMs), and 436 differentially expressed genes (DEGs) were identified. Functional analyses showed that these DEGs were associated with several processes and pathways, including "cell division," "IL-17 signaling pathway," "NOD-like receptor signaling pathway," and "cell adhesion molecules." Fibrosis-related ceRNA networks were then built, comprising five lncRNAs, seven miRNAs, and 19 DEGs. RT-qPCR and western blotting results showed that the patterns of lncRNAs (NONRATT016396.2, NONRATT001596.2, NONRATT011456.2), miRNAs (miR-10b-3p, miR-29b-3p), and mRNAs (Gng7 and Wnt2b) were consistent with sequencing analyses. CONCLUSIONS: The DELs, DEMs, and DEGs identified in this study may participate in atrial fibrosis processes, and the occurrence and progression of AF.

MiRNA21 and IL-18 levels in left atrial blood in patients with atrial fibrillation undergoing cryoablation and their predictive value for recurrence of atrial fibrillation.

PURPOSE: The recurrence of atrial fibrillation (AF) after cryoablation still needs to be prioritized, including discriminating predictive indicators. METHODS: Eighty-seven patients aged 43-83 years who underwent cryo-balloon ablation were divided into paroxysmal atrial fibrillation (PAF) and non-paroxysmal atrial fibrillation (non-PAF) groups. Baseline data, intraoperative index, and miRNA21, IL-18, NLRP3, and visfatin levels in peripheral venous blood and left atrial blood were assessed. Follow-up was performed for 6 months to observe the recurrence of AF. A Cox risk ratio model was used to analyze indicators for predicting AF recurrence. RESULTS: The non-PAF and PAF group recurrence rates of AF were statistically different (p < 0.05) at 9/22 (40.9%) and 11/65 (16.9%), respectively. Biomarker levels in the left atrial blood were higher in the non-PAF group than in the PAF group (p < 0.05). The effects of non-PAF and levels of miRNA21 and IL-18 in left atrial serum on the recurrence of AF after cryoablation statistically differed (p < 0.05). CONCLUSION: The levels of miRNA21 and IL-18 were higher in left atrial blood than in peripheral blood, which may be related to the severity of AF and recurrence of AF after cryoablation.

Clinical efficacy of "ICE-FIRE" ablation for non-paroxysmal atrial fibrillation.

PURPOSE: Catheter ablation is less successful for non-paroxysmal atrial fibrillation (NPAF) according to numerous follow-up studies. The choice of ablation strategy for patients with NPAF remains controversial. The objective of the study was to explore the clinical efficacy of the "ICE-FIRE" ablation. METHODS: Ninety NPAF patients were enrolled. Patients were randomly divided into RF (treated with circumferential pulmonary vein isolation (CPVI) and additional substrate modification by radiofrequency ablation) group and I-F (treated with CPVI by cryoablation and additional substrate modification by radiofrequency ablation) group. After CPVI and cardioversion to sinus rhythm, high-density mapping was performed. Eight-one of 90 participants restored to sinus rhythm. Seventy-four of 81 NPAF patients showed low-voltage zone. Substrates with low-voltage zone were targeted for further modification. Participants were followed at baseline, 3, 6, 9, and 12 months after the initial ablation. RESULTS: The I-F group shared more X-ray exposure (I-F, 264.4 ± 97.4 mGy; RF, 224.9 ± 62.0 mGy; P = 0.039) and less duration of the procedure (I-F, 150.3 ± 27.5 min; RF, 174.2 ± 38.5 min; P = 0.003) compared to RF group. The freedom from atrial arrhythmia recurrence at 12 months post-ablation was similar between the RF and I-F groups (RF, 57.1%; I-F, 71.8%; P = 0.197). However, I-F group experienced lower rehospitalization rate of AF recurrence (RF, 42.9%; I-F, 20.5%; P = 0.038). CONCLUSIONS: In NPAF patients requiring substrate mapping and modification, the "ICE-FIRE" ablation demonstrated non-inferior clinical efficacy and lower rehospitalization rate of AF recurrence when compared with pure radiofrequency ablation strategy.

Screening and functional analysis of differentially expressed lncRNAs in rapid atrial pacing dog atrial tissue.

PURPOSE: Atrial fibrillation (AF) is one of the most commonly sustained arrhythmias in clinical practice. Long non-coding RNAs (lncRNAs) are gene regulatory elements involved in the development of several diseases. We aimed to explore the expression characteristics of lncRNAs associated with AF. METHODS: We randomly assigned 12 adult healthy mongrel dogs into a control group and an atrial pacing group. Atrial pacing stimulation was performed at a high frequency of 500 beats per min for 14 consecutive days in the atrial pacing group. HE and Masson staining were used to detect rapid atrial pacing induced atrial fibrosis. Total RNA extraction was performed on dog atrial tissues and was used for high-throughput sequencing of lncRNAs. RESULTS: A total of 10,310 lncRNAs were detected, and 33 differentially expressed lncRNAs were screened. Among them, 19 lncRNAs were upregulated in the atrial pacing group, and 14 lncRNAs were downregulated. Gene Ontology (GO) classification, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and interaction networks showed that AF-related lncRNAs participate in the regulation of AF in diverse biological processes, cellular components, molecular functions, signaling pathways, and complex interactions with miRNAs and mRNAs. Five differentially expressed lncRNAs were selected for RT-PCR validation, and the verification results were consistent with the results of lncRNA sequencing. CONCLUSIONS: In summary, our study enhances our understanding of the biological functions of AF-related lncRNAs by screening and analyzing differentially expressed lncRNAs, and the results help to enrich the theoretical basis for the treatment of atrial fibrillation.

Biomarkers for Predicting Left Atrial or Left Atrial Appendage Thrombus in Anticoagulated Patients with Nonvalvular Atrial Fibrillation.

PURPOSE: Although atrial fibrillation (AF) is often associated with thromboembolic complications, there is no definite biomarker for detecting the presence of thrombi in the left atrial (LA) or left atrial appendage (LAA) in patients with nonvalvular atrial fibrillation (NVAF). METHODS: NVAF patients who underwent transesophageal echocardiography (TEE) to evaluate LA/LAA thrombus and spontaneous echo contrast (SEC) before AF ablation were included. Multivariate logistic regression and receiver operating characteristic curve (ROC) analyses were performed to explore the independent risk factors of LA/LAA thrombus and indicate the best cutoff point. RESULTS: Of the 260 consecutive subjects (mean age: 63.67 ± 9.39 years; 42% women), 45 (17.3%) patients were with LA/LAA thrombus, 131 (50.4%) were with SEC, and 84 (32.3%) were with neither thrombus nor SEC. The results of multivariate logistic regression analysis showed that N-terminal pro-B-type natriuretic peptide (NT-proBNP) (OR, 2.179; 95% CI: 1.191-3.987; p=0.012) and red cell distribution width (RDW) (OR, 2.398; 95% CI: 1.075-5.349; p=0.033) were independently correlated with the presence of LA/LAA thrombus but not D-dimer (OR, 0.999; 95% CI: 0.998-1.000; p=0.210). When all patients were divided into four groups based on the combination between RDW (cutoff value: 12.95%) and NT-proBNP levels (cutoff value: 368.9 ng/L), the rate of LA/LAA thrombus was the highest in the high RDW and NT-proBNP group. CONCLUSION: In anticoagulation patients with NVAF, elevated NT-proBNP and RDW are related to LA/LAA thrombus. Therefore, these might be considered as useful prognostic markers in the management and treatment of NVAF patients.

Combined treatment with valsartan and fluvastatin to delay disease progression in nonpermanent atrial fibrillation with hypertension: A clinical trial.

BACKGROUND: Atrial fibrillation (AF) is a complex cardiac arrhythmia in clinical practice with increasing incidence. However, the effects of statins on patients with AF are not quite clear. HYPOTHESIS: To investigate the protective effect of calcium channel blocker (CCB) and valsartan combined fluvastatin on hypertension (HTN) patients with nonpermanent AF. METHODS: In three and a half years, 189 cases of patients diagnosed as HTN combining nonpermanent AF by eight medical centers, were recruited and randomly assigned to four groups with varied treatments: CCB group; CCB + statin group; valsartan group; and valsartan + statin group. The four groups were followed up for 24 months. The 7-day Holter ultrasound echocardiography (UCG) and biochemical indexes were completed at preset time nodes respectively. RESULTS: After 24 months of follow-up, 178 patients completed the study. Compared with CCB group, the blood lipid level, inflammatory index, ultrasonic index and electrocardiographic measurement results of CCB + statin group, valsartan group and valsartan + statin group were improved in different degrees and had statistical significance (P < .05 or P < .01). Furthermore, the improvement trend of CCB + statin group and valsartan + statin group was more obvious. CONCLUSIONS: The results indicated that valsartan can reduce AF load and recurrence rate, and delay the progression of nonpermanent AF to permanent AF in multiple ways, and the effect of combination of valsartan and fluvastatin is more significant. These results provide a new direction for the integrated upstream control strategy of AF.

Gender-specific associations of CD36 polymorphisms with the lipid profile and susceptibility to premature multi-vessel coronary artery heart disease in the Northern Han Chinese.

BACKGROUND: The aim of the present study was to detect potential gender-specific associations between some common CD36 single nucleotide polymorphisms (SNPs) and the lipid profile, as well as the susceptibility to premature multi-vessel coronary artery heart disease (CHD) in the Han population of Northern China. METHODS: A systematic three-step study process was employed to detect associations between CD36 gene variants and blood lipid profiles, as well as premature multi-vessel CHD in a gender-specific manner. RESULTS: The current study documented the following novel findings: (I) the full population-based association study in 329 Northern Han Chinese showed that four common CD36 polymorphisms were significantly related to extreme lipid profiles, with statistically significant effects based on gender interactions (rs1049673: P = 0.001; rs7755: P = 0.008; rs3211956: P = 0.034; and rs3173798: P = 0.004); (ii) these statistically significant effects could be decomposed into statistically significant atherogenic effects in males, but non-significant non-atherogenic effects in females; (iii) the results of logistic regression analysis indicated that current smoking status, low density lipoprotein cholesterol (LDL-C) levels, and type-2 diabetes were independent risk factors for premature multi-vessel CHD phenotype (P < 0.0001). CONCLUSIONS: Four common CD36 polymorphisms (rs1049673, rs7755, rs3211956, and rs3173798) were identified to be significantly associated with extreme lipid profiles and had statistically opposite gender-specific clinical lipid profile effects. Thus, the 3'-untranslated regions (3'-UTR) CD36 SNPs could be a novel target for metabolic abnormalities in males of the Han nationality from Northern China.

MicroRNA-124 inhibits macrophage cell apoptosis via targeting p38/MAPK signaling pathway in atherosclerosis development.

The objective of this study is to characterize the function of microRNA (miR)-124 in the process of coronary artery disease (CAD). Eighty patients, including 40 CAD patients and 40 non-CAD control patients were enrolled in this study. Atherosclerosis model was established in vivo in ApoE-/- mice and in vitro in RAW264.7 cells. Expression of miR-124 and p38 in patients, animal models and cell models were measured by qRT-PCR, western blot and immunohistochemistry assay. Overexpression or suppression of miR-124 was introduced in vitro and in vivo and the expression levels of p38, miR-124, pro- and anti-inflammatory cytokines, and pro- and anti-apoptotic factors were examined. Results showed that miR-124 was decreased, while p38 was increased in CAD patients and atherosclerosis models compared with control group. MiR-124 could target p38 by binding its 3' untranslated region and negatively regulated the protein expression of p38. Overexpression of miR-124 increased the expression of anti-inflammatory cytokines, reduced the expression of pro- inflammatory cytokines, and inhibited macrophage apoptosis. MiR-124 overexpression may be a promising treatment for atherosclerosis and CAD via inhibiting p38.

[Role of probucol in preventing contrast induced acute kidney injury after coronary interventional procedure: a randomized trial].

OBJECTIVE: Contrast induced acute kidney injury (CIAKI) is a significant clinical problem. We, therefore, performed a prospective, randomized trial to investigate the role of probucol in the prevention of CIAKI in patients with unstable angina pectoris (UAP) undergoing percutaneous coronary angiography (CAG) and interventions (PCI). METHODS: We studied 205 patients with UAP, who underwent CAG or PCI prospectively. Patients were randomly assigned to probucol group (n = 102) and control group (n = 103). In the probucol group, the patients received probucol tablets 500 mg b.i.d for 3 days before and after intervention. All the patients, after intervention, underwent hydration with intravenous saline at a rate of 1 ml per kilogram of body weight per hour for 12 hours. RESULTS: Patients were well-matched with no significant difference at baseline in majority measured parameters between two groups. CIAKI occurred in 23 of the 205 (11.22%) patients. Multivariate logistic regression was used to identify correlates of CIAKI and clinical data. CIAKI was most strongly associated with Scr > or = 132.6 micromol/L (OR = 21.11, 95%CI 1.95 - 56.06, P < 0.001), Ccr < 60 ml/min (OR = 4.19, 95%CI 1.94 - 9.05, P < 0.001), heart function > class II (OR = 6.23, 95%CI 2.73 - 14.21, P < 0.001), Diabetes (OR = 2.049, 95%CI 1.19 - 5.25, P < 0.001), age > or = 70 yrs (OR = 3.52, 95%CI 1.66 - 7.43, P < 0.001), coronary artery calcification shown by CAG (OR = 4.29, 95%CI 1.99 - 9.24, P < 0.001). The rate of CIAKI in probucol groups was slightly lower compared with control group (7.84% vs. 14.56%), without significant difference. The post-procedure mean peak of Scr [(101.62 +/- 42.98) micromol/L vs. (117.67 +/- 68.77) micromol/L, P = 0.047] and the post-procedure increasing Scr from baseline (DeltaScr) [(13.49 +/- 19.61) micromol/L vs. (22.50 +/- 18.31) micromol/L, P = 0.001] in the probucol group decreased significantly compared with that of control group. CONCLUSION: Prophylactic treatment with probucol 500 mg b.i.d during periprocedural stage in patients with UAP has preventing role against CIAKI after cardiac catheterization.