Effect of Total SMS Activity on LDL Catabolism in Mice.

BACKGROUND: Sphingomyelin (SM) and cholesterol are 2 key lipid partners on cell membranes and on lipoproteins. Many studies have indicated the influence of cholesterol on SM metabolism. This study examined the influence of SM biosynthesis on cholesterol metabolism. METHODS: Inducible global Sms1 KO (knockout)/global Sms2 KO mice were prepared to evaluate the effect of whole-body SM biosynthesis deficiency on lipoprotein metabolism. Tissue cholesterol, SM, ceramide, and glucosylceramide levels were measured. Triglyceride production rate and LDL (low-density lipoprotein) catabolism were measured. Lipid rafts were isolated and LDL receptor mass and function were evaluated. Also, the effects of exogenous sphingolipids on hepatocytes were investigated. RESULTS: We found that total SMS (SM synthase) depletion significantly reduced plasma SM levels. Also, the total deficiency significantly induced plasma cholesterol, apoB (apolipoprotein B), and apoE (apolipoprotein E) levels. Importantly, total SMS deficiency, but not SMS2 deficiency, dramatically decreased LDL receptors in the liver and attenuated LDL uptake through the receptor. Further, we found that total SMS deficiency greatly reduced LDL receptors in the lipid rafts, which contained significantly lower SM and significantly higher glucosylceramide, as well as cholesterol. Furthermore, we treated primary hepatocytes and Huh7 cells (a human hepatoma cell line) with SM, ceramide, or glucosylceramide, and we found that only SM could upregulate LDL receptor levels in a dose-dependent fashion. CONCLUSIONS: Whole-body SM biosynthesis plays an important role in LDL cholesterol catabolism. The total SMS deficiency, but not SMS2 deficiency, reduces LDL uptake and causes LDL cholesterol accumulation in the circulation. Given the fact that serum SM level is a risk factor for cardiovascular diseases, inhibiting SMS2 but not SMS1 should be the desirable approach.

Potential Application of Pulsed Field Ablation in Ventricular Arrhythmias.

Pulsed field ablation (PFA) is a new ablative method for the therapy of arrhythmia. Recent preclinical and clinical studies have already demonstrated the feasibility and safety of PFA for the treatment of atrial fibrillation (AF). However, the application of PFA may not be limited to the above fields. There are some data on the application of PFA on ventricular arrhythmias (VAs), such as ventricular fibrillation (VF) and ventricular tachycardia (VT). Further, a case report about PFA has been published recently, in which PFA was successfully applied to the ablation of premature ventricular contractions (PVCs) from the right ventricular outflow tract. Thus, we aimed to review recent research findings of PFA in ventricular ablation and evaluate the possibility of its application in VAs.

Emergent Zero-Fluoroscopy Mapping and Thoracoscopic Ectomy of Appendage in Pregnant Women with Life-Threatening Atrial Tachycardia: A Case Report and Literature Review.

Background: Focal atrial tachycardia (AT) originating from the right atrial appendage (RAA), often persistent and refractory, is clinically rare in pregnant woman, and the therapy is much more challenging. We report that a pregnant woman presented with hypotension due to persistent and refractory atrial tachycardia and was successfully cured by a multidisciplinary treatment (MDT) approach, consisting of a combination of zero-fluoroscopy mapping and thoracoscopic atrial appendectomy. We also carried out a literature review of this topic. Methods and Results: A 26-year-old woman in pregnancy at 21 weeks presented with severe palpitation and hypotension due to persistent rapid supraventricular tachycardia (SVT). Since adenosine triphosphate could not terminate the tachycardia, a catheter ablation procedure was planned and finally canceled when the zero-fluoroscopy mapping using Carto 3TM system revealed an atrial tachycardia originating from the RAA. Thoracoscopic RAA ectomy was recommended after multidisciplinary consultation and successfully performed without fluoroscopy. EnsiteTM velocity mapping system was used for accurately locating the origin of the arrhythmia during ectomy. The woman finally produced a healthy baby during follow-up. Conclusions: Focal AT originating from appendage in pregnant patients can be persistent, refractory, and life-threatening; traditional strategies, such as medicine or catheter ablation, are limited in this situation. MDT measures, using a thoracoscopic ectomy and zero-fluoroscopy three-dimensional electroanatomical mapping technique, is minimally invasive and a promising strategy.

Characteristics and Risk Factors of Pulmonary Hypertension in Patients With Hyperthyroidism.

OBJECTIVE: This study aimed to comprehensively assess the characteristics and risk factors of hyperthyroidism with pulmonary hypertension (PH). METHODS: This was a retrospective cross-sectional analysis of 315 consecutive patients with hyperthyroidism admitted to the endocrinology department of Tongji Hospital from February 2016 to December 2017. PH was defined as a pulmonary arterial systolic pressure above 35 mm Hg measured by echocardiography. RESULTS: Among the 315 patients, 208 were females, the median age was 42 (30-51) years, and the median disease duration was 12 (3-48) months. Thirty-five percent (111/315) of patients were identified with PH. Patients with hyperthyroidism and PH showed significantly higher serum concentrations of free thyroxine (FT4), free triiodothyronine, thyroid receptor antibodies, total bilirubin (TB), direct and indirect bilirubin, lower serum levels of hemoglobin and creatinine, and more severe cardiac load (P < .05 for each) compared with patients without PH. Levels of serum FT4, free triiodothyronine, thyroid receptor antibodies, and thyroid peroxidase antibody were different among groups of patients with different levels of pulmonary arterial systolic pressure (P < .05 for each). Multivariate logistic regression analysis indicated that serum FT4 (odds ratio, 1.02; 95% CI, 1.01-1.04; P = .004) and TB (OR, 1.03; 95% CI, 1.00-1.06; P = .030) were independent risk factors for PH in patients with hyperthyroidism. CONCLUSION: Elevated serum FT4 and TB levels may be independent risk factors for PH in patients with hyperthyroidism and valuable indicators for the identification and treatment of patients with PH and hyperthyroidism.

Increased lipoxygenase and decreased cytochrome P450s metabolites correlated with the incidence of diabetic nephropathy: Potential role of eicosanoids from metabolomics in type 2 diabetic patients.

Diabetic nephropathy (DN) is the major cause of chronic kidney disease and end-stage renal disease. Previous studies have demonstrated that long-chain omega-3 polyunsaturated fatty acids (PUFAs) might have therapeutic potential in reducing proteinuria in DN. However, the local level of eicosanoids derived from PUFAs in the plasma of DN patients remains unclear. This work aims to study the eicosanoid profile difference in plasma of DN patients and type 2 diabetes (T2D) without DN. A total of 27 T2D patients with similar diabetic duration were recruited and divided into T2D+DN group and T2D+NDN (non-DN) group based on urinary albumin excretion (UAE) detection. Using LC-MS/MS-based metabolomics, DN patients showed increased level of lipoxygenase (LOX) metabolites (5-HETE and LTB4) and decreased levels of eicosanoids derived according to the cytochrome P450s (CYP450) metabolic pathway (5,6-DHET; 14,15-DHET and 9,10-diHOME). Receiver operating characteristics and logistic regression analysis revealed increased level LOX metabolites and decreased level of CYP450 metabolites were significantly correlated with the incidence of DN in T2D patients. LOX and CYP450 metabolites correlated with DN incidence in T2D patients, which might be treatment targets for DN in T2D patients.

Update on high-power short-duration ablation for pulmonary vein isolation.

Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation. However, this procedure remains complex and time-consuming, and the recurrence of AF after PVI is still unsatisfactory. Current technologies have improved our knowledge of the association between radiofrequency lesion creation and ablation parameters (power and duration), which triggered the development of high-power short-duration (HPSD). During the past decade, several preclinical and clinical studies have been conducted to confirm the feasibility, safety, and outcome of PVI ablation with HPSD or very high-power short-duration (vHPSD) settings, which increased electrophysiologists' interests in the utility of HPSD strategies. This paper describes the theoretical basis and recent research findings of HPSD or vHPSD ablation and summarizes the state-of-the-art evidence behind the role of this strategy in PVI.

Cardiac-Specific Caveolin-3 Overexpression Prevents Post-Myocardial Infarction Ventricular Arrhythmias by Inhibiting Ryanodine Receptor-2 Hyperphosphorylation.

INTRODUCTION: Ventricular arrhythmia is the most important risk factor for sudden cardiac death (SCD) after acute myocardial infarction (MI) worldwide. However, the molecular mechanisms underlying these arrhythmias are complex and not completely understood. OBJECTIVE: Here, we evaluated whether caveolin-3 (Cav3), the structural protein of caveolae, plays an important role in the therapeutic strategy for ventricular arrhythmias. METHODS: A model of cardiac-specific overexpression of Cav3 was established to evaluate the incidence of ventricular arrhythmias after MI in mice. Ca2+ imaging was employed to detect the propensity of adult murine cardiomyocytes to generate arrhythmias, and immunoprecipitation and immunofluorescence were used to determine the relationship of proteins. Additionally, qRT-PCR and western blotting were used to detect the mRNA and protein expression. RESULTS: We found that cardiac-specific overexpression of Cav3 delivered by a recombinant adeno-associated viral vector reduced the incidence of ventricular arrhythmias and SCD after MI in mice. Ca2+ imaging and western blotting revealed that overexpression of Cav3 reduced diastolic spontaneous Ca2+ waves by inhibiting the hyperphosphorylation of ryanodine receptor-2 (RyR2) at Ser2814, rather than at Ser2808, compared to in rAAV-red fluorescent protein control mice. Furthermore, we demonstrated that Cav3-regulated RYR2 hyperphosphorylation relied on plakophilin-2 in hypoxia-stimulated cultured cardiomyocytes by western blotting, immunoprecipitation, and immunofluorescence in vitro. CONCLUSIONS: Our results suggested a novel role for Cav3 in the prevention of ventricular arrhythmias, thereby identifying a new target for preventing SCD after MI.

Zero-fluoroscopy approach for ablation of supraventricular tachycardia using the Ensite NavX system: a multicenter experience.

BACKGROUND: Three-dimensional electroanatomic mapping systems have demonstrated a significant reduction in radiation exposure during radiofrequency catheter ablation procedures. We aimed to investigate the safety, feasibility and efficacy of a completely zero-fluoroscopy approach for catheter ablation of supraventricular tachycardia using the Ensite NavX navigation system compared with a conventional fluoroscopy approach. METHODS: A multicenter prospective non-randomized registry study was performed in seven centers from January 2013 to February 2018. Consecutive patients referred for catheter ablation of supraventricular tachycardia were assigned either to a completely zero-fluoroscopic approach (ZF) or conventional fluoroscopy approach (CF) according to the operator's preference. Patients with atrial tachycardia were excluded. RESULTS: Totally, 1020 patients were enrolled in ZF group; 2040 patients ablated by CF approach were selected for controls. There was no significant difference between the zero-fluoroscopy group and conventional fluoroscopy group as to procedure time (60.3 ± 20.3 vs. 59.7 ± 22.6 min, P = 0.90), immediate success rate of procedure (98.8% vs. 99.2%, P = 0.22), arrhythmia recurrence (0.4% vs. 0.5%, P = 0.85), total success rate of procedure (98.4% vs. 98.8%, P = 0.39) or complications (1.1% vs. 1.5%, P = 0.41). Compared with the conventional fluoroscopy approach, the zero-fluoroscopy approach provided similar outcomes without compromising the safety or efficacy of the procedure. CONCLUSION: The completely zero-fluoroscopy approach demonstrated safety and efficacy comparable to a conventional fluoroscopy approach for catheter ablation of supraventricular tachycardia, and mitigated radiation exposure to both patients and operators. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03042078; first registered February 3, 2017; retrospectively registered.

Progress in zero-fluoroscopy implantation of cardiac electronic device.

Fluoroscopy is the imaging modality routinely used for cardiac device implantation. Due to the rising concern regarding the harmful effects of radiation exposure to both the patients and operation staffs, many efforts have been made to develop alternative techniques to achieve zero-fluoroscopy implantation. In this review, we describe the different methods aimed at avoiding the application of fluoroscopy in recent years, and evaluate their feasibility and safety in cardiac electronic device implantation.

Effect of green tea consumption on blood lipids: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Strong epidemiologic evidence indicates that green tea intake is protective against hyperlipidemia; however, randomized controlled studies have presented varying results. In the present study, we aimed to conduct a literature review and meta-analysis to assess the effect of green tea on blood lipids. METHODS: PubMed, Embase, and the Cochrane Library were electronically explored from inception to September 2019 for all relevant studies. Random effect models were used to estimate blood lipid changes between green tea supplementation and control groups by evaluating the weighted mean differences (WMD) with 95% confidence intervals (CIs). The risk of bias for study was assessed using the Cochrane tool. Publication bias was evaluated using funnel plots and Egger's tests. RESULTS: Thirty-one trials with a total of 3321 subjects were included in the meta-analysis. In general, green tea intake significantly lowered the total cholesterol (TC); WMD: - 4.66 mg/dL; 95% CI: - 6.36, - 2.96 mg/dL; P < 0.0001) and low-density lipoprotein (LDL) cholesterol (WMD:- 4.55 mg/dL; 95% CI: - 6.31, - 2.80 mg/dL; P < 0.0001) levels compared with those in the control. Green tea consumption did not affect high-density lipoprotein (HDL) cholesterol; however, it reduced the triglycerides compared with that in the control (WMD: - 3.77 mg/dL; 95% CI: - 8.90, 1.37 mg/dL; P = 0.15). In addition, significant publication bias from funnel plots or Egger's tests was not evident. CONCLUSIONS: Collectively, consumption of green tea lowers LDL cholesterol and TC, but not HDL cholesterol or triglycerides in both normal weight subjects and those who were overweight/obese; however, additional well-designed studies that include more diverse populations and longer duration are warranted.

Zero-fluoroscopy permanent pacemaker implantation using Ensite NavX system: Clinical viability or fanciful technique?

BACKGROUND: Fluoroscopy is the imaging modality routinely used for cardiac device implantation and electrophysiological procedures. Due to the rising concern regarding the harmful effects of radiation exposure to both the patients and operation staffs, novel 3D mapping systems have been developed and implemented in electrophysiological procedure for the navigation of catheters inside the heart chambers. Their applicability in cardiac device implantation has been rarely reported. Our aim is to evaluate the feasibility and safety of permanent pacemaker implantation without fluoroscopy. METHODS AND RESULTS: From January 2012 to June 2016, six patients (50 ± 15 years, four of six were female, one of who was at the 25th week of gestation) who underwent permanent pacemaker implantation were included (zero-fluoroscopy group). Data from 20 consecutive cases of implantation performed under fluoroscopy guidance were chosen as a control group (fluoroscopy group). Total implantation procedure time for single-chamber pacemaker was 51.3 ± 13.1 minutes in the zero-fluoroscopy group and 42.6 ± 7.4 minutes in the fluoroscopy group (P  =  0.155). The implantation procedural time for a dual-chamber pacemaker was 88.3 ± 19.6 minutes and 67.3 ± 7.6 minutes in the zero-fluoroscopy and fluoroscopy groups (P  =  0.013), respectively. No complications were observed during the procedure and the follow-up in the two groups, and all pacemakers worked with satisfactory parameters. CONCLUSION: Ensite NavX system can be used as a reliable and safe zero-fluoroscopy approach for the implantation of single- or dual-chamber permanent pacemakers in specific patients, such as pregnant women or in extreme situations when the x-ray machine is not available.

Role of cytochrome P450 epoxygenase-dependent arachidonic acid metabolites in kidney physiology and diseases.

Kidney diseases are important causes of mortality world widely. Renal microvascular dysfunction plays a pivotal role in the development of kidney diseases. Pharmacological and biochemical tools have been used to conduct detailed studies on the metabolization of arachidonic acid by cytochrome P450 (CYP450) in renal microvasculature. CYP450 epoxygenase metabolites epoxyeicosatrienoic acids (EETs) are mainly produced in renal microvessels. EETs exhibit renoprotective effects through vasodilation, anti-hypertension, anti-apoptosis and anti-inflammation, and were reported as therapeutic targets of renal diseases. However, the ability of the kidney in generating EETs is reduced in renal diseases. Recently, the studies from transgenic animal overexpressing CYP450 epoxygenases and application of soluble epoxide hydrolase inhibitors revealed that increasing of EETs exhibits renoprotective effects in vivo. The present review focuses on the protective mechanisms of EETs in kidney physiology and diseases.

CYP2J2 overexpression attenuates nonalcoholic fatty liver disease induced by high-fat diet in mice.

Cytochrome P-450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) exert diverse biological activities, which include potent vasodilatory, anti-inflammatory, antiapoptotic, and antioxidatant effects, and cardiovascular protection. Liver has abundant epoxygenase expression and high levels of EET production; however, the roles of epoxygenases in liver diseases remain to be elucidated. In this study, we investigated the protection against high-fat diet-induced nonalcoholic fatty liver disease (NAFLD) in mice with endothelial-specific CYP2J2 overexpression (Tie2-CYP2J2-Tr). After 24 wk of high-fat diet, Tie2-CYP2J2-Tr mice displayed attenuated NAFLD compared with controls. Tie2-CYP2J2-Tr mice showed significantly decreased plasma triglyceride levels and liver lipid accumulation, improved liver function, reduced inflammatory responses, and less increase in hepatic oxidative stress than wild-type control mice. These effects were associated with inhibition of NF-κB/JNK signaling pathway activation and enhancement of the antioxidant defense system in Tie2-CYP2J2-Tr mice in vivo. We also demonstrated that 14,15-EET treatment protected HepG2 cells against palmitic acid-induced inflammation and oxidative stress. 14,15-EET attenuated palmitic acid-induced changes in NF-κB/JNK signaling pathways, malondialdehyde generation, glutathione levels, reactive oxygen species production, and NADPH oxidase and antioxidant enzyme expression in HepG2 cells in vitro. Together, these results highlight a new role for CYP epoxygenase-derived EETs in lipotoxicity-related inflammation and oxidative stress and reveal a new molecular mechanism underlying EETs-mediated anti-inflammatory and antioxidant effects that could aid in the design of new therapies for the prevention and treatment of NAFLD.

CYP2J2-derived epoxyeicosatrienoic acids protect against doxorubicin-induced cardiotoxicity by reducing oxidative stress and apoptosis via activation of the AMPK pathway.

Objective: Despite the widespread use of doxorubicin (DOX) in chemotherapy, it can cause cardiotoxicity, which severely limits its potential clinical use. CYP2J2-derived epoxyeicosatrienoic acids (EETs) exert cardioprotective effects by maintaining cardiac homeostasis. The roles and latent mechanisms of EETs in DOX cardiotoxicity remain uncertain. We investigated these aspects using mouse tissue and cell culture models. Methods: C57BL/6J mice were injected with rAAV9-CYP2J2 or a control vector via the caudal vein. A five-week intraperitoneal course of DOX (5 mg/kg per week) was administered. After pretreatment with 14,15-EET, H9C2 cells were treated for 24-h with DOX, to use as a cell model to verify the role of EETs in cardiotoxicity in vitro. Results: CYP2J2 overexpression mitigated DOX-induced cardiotoxicity, as shown by the diminished cardiac injury marker levels, improved heart function, reduced oxidative stress, and inhibition of myocardial apoptosis in vivo. These protective roles are associated with the enhancement of antioxidant and anti-apoptotic abilities and the activation of the AMPK pathway. 14,15-EET suppresses DOX-induced oxidative stress, mitochondrial dysfunction, and apoptosis in H9C2 cells. AMPK knockdown partially abolished the cardioprotective effects of 14,15-EET against oxidative damage and apoptosis in DOX-treated cells, suggesting that AMPK is responsible for EET-mediated protection against cardiotoxicity. Conclusion: CYP2J2-derived EETs confer myocardial protection against DOX-induced toxicity by activating the AMPK pathway, which reduces oxidative stress, mitochondrial dysfunction, and apoptosis.

A Large-Scale Network Construction and Lightweighting Method for Point Cloud Semantic Segmentation.

To significantly enhance the performance of point cloud semantic segmentation, this manuscript presents a novel method for constructing large-scale networks and offers an effective lightweighting technique. First, a latent point feature processing (LPFP) module is utilized to interconnect base networks such as PointNet++ and Point Transformer. This intermediate module serves both as a feature information transfer and a ground truth supervision function. Furthermore, in order to alleviate the increase in computational costs brought by constructing large-scale networks and better adapt to the demand for terminal deployment, a novel point cloud lightweighting method for semantic segmentation network (PCLN) is proposed to compress the network by transferring multidimensional feature information of large-scale networks. Specifically, at different stages of the large-scale network, the structure and attention information of the point features are selectively transferred to guide the compressed network to train in the direction of the large-scale network. This paper also solves the problem of representing global structure information of large-scale point clouds through feature sampling and aggregation. Extensive experiments on public datasets and real-world data demonstrate that the proposed method can significantly improve the performance of different base networks and outperform the state-of-the-art.

Effect of Total Sphingomyelin Synthase Activity on Low Density Lipoprotein Catabolism in Mice.

Background: Sphingomyelin (SM) and cholesterol are two key lipid partners on cell membranes and on lipoproteins. Many studies have indicated the influence of cholesterol on SM metabolism. This study examined the influence of SM biosynthesis on cholesterol metabolism. Methods: Inducible global Sms1 KO/global Sms2 KO mice were prepared to evaluate the effect of whole-body SM biosynthesis deficiency on lipoprotein metabolism. Tissue cholesterol, SM, ceramide, and glucosylceramide levels were measured. TG production rate and LDL catabolism were measured. Lipid rafts were isolated and LDL receptor mass and function were evaluated. Also, the effects of exogenous sphingolipids on hepatocytes were investigated. Results: We found that total SMS depletion significantly reduced plasma SM levels. Also, the total deficiency significantly induced plasma cholesterol, apoB, and apoE levels. Importantly, total SMS deficiency, but not SMS2 deficiency, dramatically decreased LDL receptors in the liver and attenuated LDL uptake through the receptor. Further, we found that total SMS deficiency greatly reduced LDL receptors in the lipid rafts which contained significantly lower SM and significantly higher glucosylceramide as well as cholesterol. Furthermore, we treated primary hepatocytes and Huh7 cells (a human hepatoma cell line) with SM, ceramide, or glucosylceramide, and we found that only SM could up-regulate LDL receptor levels in a dose-dependent fashion. Conclusions: Whole-body SM biosynthesis plays an important role in LDL-cholesterol catabolism. The total SMS deficiency, but not SMS2 deficiency, reduces LDL uptake and causes LDL-cholesterol accumulation in the circulation. Given the fact that serum SM level is a risk factor for cardiovascular diseases, inhibiting SMS2 but not SMS1 should be the desirable approach.

Genetic disruption of soluble epoxide hydrolase is protective against streptozotocin-induced diabetic nephropathy.

Cytochrome P-450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which play important roles in regulating cardiovascular functions. The anti-inflammatory, antiapoptotic, proangiogenic, and antihypertensive properties of EETs suggest a beneficial role for EETs in diabetic nephropathy. Endogenous EET levels are maintained by a balance between synthesis by CYP epoxygenases and hydrolysis by epoxide hydrolases into physiologically less active dihydroxyeicosatrienoic acids. Genetic disruption of soluble epoxide hydrolase (sEH/EPHX2) results in increased EET levels through decreased hydrolysis. This study investigated the effects of sEH gene disruption on diabetic nephropathy in streptozotocin-induced diabetic mice. Streptozotocin-induced diabetic manifestations were attenuated in sEH-deficient mice relative to wild-type controls, with significantly decreased levels of Hb A(1c), creatinine, and blood urea nitrogen and urinary microalbumin excretion. The sEH-deficient diabetic mice also had decreased renal tubular apoptosis that coincided with increased levels of antiapoptotic Bcl-2 and Bcl-xl, and decreased levels of the proapoptotic Bax. These effects were associated with activation of the PI3K-Akt-NOS3 and AMPK signaling cascades. sEH gene inhibition and exogenous EETs significantly protected HK-2 cells from TNFα-induced apoptosis in vitro. These findings highlight the beneficial role of the CYP epoxygenase-EETs-sEH system in the pathogenesis of diabetic nephropathy and suggest that the sEH inhibitors available may be potential therapeutic agents for this condition.

Caveolin-3 and Arrhythmias: Insights into the Molecular Mechanisms.

Caveolin-3 is a muscle-specific protein on the membrane of myocytes correlated with a variety of cardiovascular diseases. It is now clear that the caveolin-3 plays a critical role in the cardiovascular system and a significant role in cardiac protective signaling. Mutations in the gene encoding caveolin-3 cause a broad spectrum of clinical phenotypes, ranging from persistent elevations in the serum levels of creatine kinase in asymptomatic humans to cardiomyopathy. The influence of Caveolin-3(CAV-3) mutations on current density parallels the effect on channel trafficking. For example, mutations in the CAV-3 gene promote ventricular arrhythmogenesis in long QT syndrome 9 by a combined decrease in the loss of the inward rectifier current (IK1) and gain of the late sodium current (INa-L). The functional significance of the caveolin-3 has proved that caveolin-3 overexpression or knockdown contributes to the occurrence and development of arrhythmias. Caveolin-3 overexpression could lead to reduced diastolic spontaneous Ca2+ waves, thus leading to the abnormal L-Type calcium channel current-induced ventricular arrhythmias. Moreover, CAV-3 knockdown resulted in a shift to more negative values in the hyperpolarization-activated cyclic nucleotide channel 4 current (IHCN4) activation curve and a significant decrease in IHCN4 whole-cell current density. Recent evidence indicates that caveolin-3 plays a significant role in adipose tissue and is related to obesity development. The role of caveolin-3 in glucose homeostasis has attracted increasing attention. This review highlights the underlining mechanisms of caveolin-3 in arrhythmia. Progress in this field may contribute to novel therapeutic approaches for patients prone to developing arrhythmia.

Massive pleural effusion following high-power and short-duration radiofrequency ablation for treatment of atrial fibrillation: A case report and review of the literature.

Postpericardial injury syndrome (PPIS) is defined as pericarditis or pericardial effusion that results from recent myocardial infarction or intracardiac interventions. These symptoms typically include fever, leukocytosis, a high erythrocyte sedimentation rate, and elevated C-reactive protein levels. Additionally, pericardial effusion and pleural effusion may be present. It is considered to be a common complication in cardio-surgery with an occurrence of 3-30%. In the past 20 years, a high number of patients with atrial fibrillation have suffered from PPIS following radiofrequency catheter ablation. However, previous reports focused on identifying cardiac tamponade and pericardial effusion as their main clinical manifestations. Solitary pulmonary involvement following PPIS with the radiofrequency catheter ablation may occur. We report a case of PPIS that presented pleural effusion as the dominant feature soon after the operation and systematic review to illustrate the clinical characteristics of PPIS.

Soluble Epoxide Hydrolase Inhibition Protected against Diabetic Cardiomyopathy through Inducing Autophagy and Reducing Apoptosis Relying on Nrf2 Upregulation and Transcription Activation.

Background: Many patients with diabetes die from diabetic cardiomyopathy (DCM); however, effective strategies for the prevention or treatment of DCM have not yet been clarified. Methods: Leptin receptor-deficient (db/db) mice were treated with either the soluble epoxide hydrolase (sEH) inhibitor AUDA or vehicle alone. A virus carrying Nrf2 shRNA was used to manipulate Nrf2 expression in db/db mice. Cardiac structures and functions were analyzed using echocardiography and hemodynamic examinations. Primary cardiomyocytes cultured under high glucose and high fat (HGHF) conditions were used to conduct in vitro loss-of-function assays after culture in the presence or absence of AUDA (1 µM). Fluorescence microscopy-based detection of mCherry-GFP-LC3 was performed to assess autophagic flux. Results: The sEH inhibitor AUDA significantly attenuated ventricular remodeling and ameliorated cardiac dysfunction in db/db mice. Interestingly, AUDA upregulated Nrf2 expression and promoted its nuclear translocation in db/db mice and the HGHF-treated cardiomyocytes. Additionally, AUDA increased autophagy and decreased apoptosis in db/db mice heart. Furthermore, the administration of AUDA promoted autophagic flux and elevated LC3-II protein level in the presence of bafilomycin A1. However, AUDA-induced autophagy was abolished, and the antiapoptotic effect was partially inhibited upon Nrf2 knockdown. Conclusion: Our findings suggest that the sEH inhibitor AUDA attenuates cardiac remodeling and dysfunction in DCM via increasing autophagy and reducing apoptosis, which is relevant to activate Nrf2 signaling pathway.