Search

BACKGROUND: The assessment of interatrial septum (IAS) requires a standardized, systematic approach, including two-dimensional transthoracic echocardiography (2D TTE), 2D transesophageal echocardiography (2D TEE), and three-dimensional (3D) TEE. Although 2D TEE has been widely used for the preoperative assessment of atrial septal defect (ASD), its ability to provide reliable information is often limited due to the structural characteristics of IAS. The introduction of 3D TEE provides a unique “en face” view of IAS, which allows the visualization and accurate measurements of diameters, area, and rims of ASD. Hence, appropriate ASD imaging information is particularly important in successful transcatheter closure. METHODS: In this retrospective study, 2D TTE/TEE, and 3D TEE were performed before ASD closure, with 2D minimal and maximal diameters, areas, and residual rims being recorded. Adequate 3D TEE imaging data sets were collected and then analyzed. ASD related parameters were compared using different echocardiography. Patients who underwent ASD closure completed a clinical follow-up. RESULTS: The mean defect maximal diameter and aperture area by 3D TEE was significantly larger than that of the corresponding 2D TEE (P

Numerous previous studies have found that C-reactive protein (CRP) is associated with cardiac arrhythmia and cardiac remodeling. However, the underlying mechanisms of this association remain unclear. Sodium-calcium exchanger 1 (NCX1) serves an important role in the regulation of intracellular calcium concentration, which is closely related with cardiac arrhythmia and cardiac remodeling. The present study aimed to evaluate the effects of CRP on NCX1 and intracellular calcium concentration in cardiomyocytes. Primary neonatal mouse ventricular cardiomyocytes were cultured and treated with varying concentrations of CRP (0, 5, 10, 20 and 40 µg/ml). The cardiomyocytes were also treated with NF-κB-specific inhibitor PTDC and a specific inhibitor of the reverse NCX1 KB-R7943 before their intracellular calcium concentrations were measured. mRNA and protein expression levels of NCX1 were detected by reverse transcription-quantitative PCR and western blotting, respectively and intracellular calcium concentration was evaluated by flow cytometry. CRP treatment significantly increased mRNA and protein expression levels of NCX1 in myocytes (P=0.024), as well as intracellular calcium concentration (P=0.01). These results were significantly attenuated by the NF-κB-specific inhibitor PDTC and a specific inhibitor of the reverse NCX1, KB-R7943. CRP significantly upregulated NCX1 expression and increased intracellular calcium concentration in cardiomyocytes via the NF-κB pathway, suggesting that CRP may serve a pro-arrhythmia role via direct influence on the calcium homeostasis of cardiomyocytes.

Background Coronary atherosclerotic heart disease (CHD) is the most common cardiovascular disease and has become a leading cause of death globally. Various molecular typing methods are available for the diagnosis and treatment of tumors. However, molecular typing results are not routinely used for CHD. Methods and Results Aiming to uncover the underlying molecular features of different types of CHD, we screened the differentially expressed genes (DEGs) associated with CHD based on the Gene Expression Omnibus (GEO) data and expanded those with the NCBI‐gene and OMIM databases to finally obtain 2021 DEGs. The weighted gene co‐expression analysis (WGCNA) was performed on the candidate genes, and six distinctive WGCNA modules were identified, two of which were associated with CHD. Moreover, DEGs were mined as key genes for co‐expression based on the module network relationship. Furthermore, the differentially expressed miRNAs in CHD and interactions in the database were mined in the GEO data set to build a multifactor regulatory network of key genes for co‐expression. Based on the network, the CHD samples were further classified into five clusters and we defined FTH1, HCAR3, RGS2, S100A9, and TYROBP as the top genes of the five subgroups. Finally, the mRNA levels of FTH1, S100A9, and TYROBP were found to be significantly increased, while the expression of HCAR3 was decreased in the blood of CHD patients. We did not detect measurable levels of RGS2. Conclusion The screened core clusters of genes may be a target for the diagnosis and treatment of CHD as a molecular typing module., WGCNA was performed on CHD‐related datasets downloaded from online datebases to screened out DEGs and a multi‐factor regulatory network of key genes for co‐expression. Based on the aforementioned network, the CHD samples were further classified into 5 clusters and we defined FTH1, HCAR3, RGS2, S100A9 and TYROBP as individually top genes of 5 subgroups.

Background and aims We examined whether the inflammation resolution mediator lipoxin A4 (LXA4) inhibits foam cell formation and oxidized low-density lipoprotein (oxLDL)-induced apoptotic signaling in macrophages and the role of circulating/local LXA4 biosynthesis in atherogenesis. Methods LXA4 levels were measured by enzyme-linked immunosorbent assay. Dil-oxLDL and Dil-acLDL binding to and uptake by macrophages were evaluated by flow cytometry. Apoptosis was evaluated by TUNEL and Annexin V/PI assays. Results Circulating LXA4 levels in patients with coronary artery disease were much higher than those in respective controls. Local LXA4 levels were much lower in rabbit atherosclerotic vessel walls. Interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α) were elevated in atherosclerotic vessels. After the inflammatory stimulus (IFN-γ, TNF-α, and C-reactive protein), LXA4 synthesis decreased significantly in foam cells. LXA4 dose-dependently suppressed the expression of the cholesterol uptake genes CD36 and SR-A in macrophages, which was blocked by the LXA4 receptor antagonist BOC-2. LXA4 also inhibited oxLDL-induced CD36 upregulation, Dil-oxLDL uptake, and foam cell formation. Furthermore, LXA4 inhibited the oxLDL-activated c-Jun N-terminal kinase pathway and reduced oxLDL-induced macrophage apoptosis by inhibiting caspase-3 activation and restoring the mitochondrial membrane potential. Conclusions We found that LXA4 inhibited foam cell formation, oxLDL-induced inflammation, and apoptotic signaling in macrophages. Insufficient levels of the anti-inflammatory pro-resolution molecule LXA4 were found in rabbit atherosclerotic arteries, which might contribute to preventing inflammation resolution during atherogenesis.

Telemedicine interventions may be associated with reductions in hospital admission rate and mortality in patients with heart failure (HF). The present study is an updated analysis (as of June 30, 2016) of randomized controlled trials, where patients with HF underwent telemedicine care or the usual standard care. Data were extracted from 39 eligible studies for all-cause and HF-related hospital admission rate, length of stay, and mortality. The overall all-cause mortality (pooled OR=0.80, 95% CI 0.71 to 0.91, p

Background: Cyclophilin A (CyPA) plays an important role in the progression of atherosclerosis. Additionally, it has been reported that lysosomal function is markedly impaired in atherosclerosis induced by oxidized low-density lipoprotein (ox-LDL). As the CyPA degradation pathway remains to be elucidated, we aimed to uncover the role of lysosomes and ox-LDL in the degradation of CyPA. Methods: We exploited RNA interference (RNAi) in combination with either the lysosomal inhibitor chloroquine (CQ) or the proteasomal inhibitor MG-132 to examine CyPA turnover. We also investigated the role of ox-LDL in lysosomal function and the CyPA degradation pathway and determined whether CyPA interacts with the selective autophagy adaptor p62. Results: CQ markedly reversed the CyPA downregulation induced by RNAi and increased intracellular levels of LC3 and p62. MG-132 significantly suppressed polyubiquitinated protein degradation but did not inhibit RNAi-induced CyPA downregulation. Additionally, neither CQ nor MG-132 influenced the gene-silencing efficiency of CyPA siRNA. Moreover, ox-LDL induced cytosolic accumulation of p62 was inconsistent with increased expression of LC3-II. Meanwhile, ox-LDL inhibited RNAi-induced downregulation of CyPA. Immunofluorescence indicated colocalization of endogenous CyPA with ubiquitin and with p62 in response to CQ treatment, and co-immunoprecipitation analysis confirmed interaction between CyPA and p62. Conclusion: CyPA is degraded by a lysosome-dependent pathway that may involve p62-mediated selective autophagy. Furthermore, ox-LDL modulates the degradation of CyPA via its inhibitory role in lysosomes, contributing to increased expression of CyPA in atherosclerotic plaques.

Aims Adverse cardiovascular effects induced by peroxisome proliferator activator receptor-γ (PPAR-γ) activation were observed in clinical setting. But the underlying mechanism is unclear. Now, transgenic mice with cardiac specific peroxisome proliferator activator receptor-γ overexpression (TG-PPAR-γ) were used to explore the possible mechanisms. Materials and methods Cardiac tissues from TG-PPAR-γ mice, a PPAR-γ over-expressing human cardiomyocyte line AC16 cell, and PPAR-γ agonist-treated primary cardiomyocytes were used to evaluate the expression of cardiac calcium regulatory proteins as sarcoplasmic reticulum Ca 2 + ATPase, Na + /Ca 2 + exchanger 1, ryanodine receptor 2 and phospholamban. Intracellular Ca 2 + levels were also examined by flow cytometry and confocal microscopy with Fluo-4/AM in these cells. Key findings In this study, frequent ventricular premature contraction and polymorphic ventricular tachycardia were observed in TG-PPAR-γ but not in wild-type mice. Besides, we found the calcium regulatory proteins expression were higher in the TG-PPAR-γ mice, PPAR-γ overexpressing human cardiomyocyte line AC16 cell and PPAR-γ agonist-treated primary cardiomyocytes than the control group respectively. In addition, an increase of intracellular calcium levels and CaMKII δ expression in PPAR-γ overexpression and PPAR-γ activation group. Moreover, Inhibition of CaMKII δ could improve the intracellular calcium levels and reduce the occurrence of ventricular arrhythmia. Significance PPAR-γ over-expression perturbs the intracellular calcium homeostasis in cardiomyocytes which contribute to the ventricular arrhythmias and cardiac sudden death in TG-PPAR-γ mice.

BACKGROUND The therapeutic potential of endothelial colony-forming cells (ECFCs) may be impaired in an ischemic environment. Direct injection of ECFCs is not an effective method of rescuing the ischemic heart, but exosomes derived from these cells may be a promising therapeutic tool. However, exosomes produced under normoxia and hypoxia may not be identical. Therefore, the purpose of this study was to investigate alterations in the anti-fibrotic effects of hypoxia-treated ECFC-derived exosomes and the underlying mechanism involved. MATERIAL AND METHODS ECFCs were isolated from peripheral blood and exosomes were collected from ECFCs treated with normoxia (nor-exo) or hypoxia (hyp-exo). Effects of exosomes on cardiac fibroblast activation were evaluated in vitro. MicroRNAs (miRNAs) inside the exosomes were extracted and compared using next-generation RNA sequencing. Predicted target mRNAs of miR-10b-5p were validated using a dual-luciferase reporter gene assay method. RESULTS Nor-exo significantly ameliorated cardiac fibroblast activation in vitro. These effects were attenuated in the hyp-exo-treated group. miR-10b-5p was enriched in nor-exo but not in hyp-exo. Dual-luciferase reporter gene assay found that both SMAD-specific E3 ubiquitin protein ligase 1 (Smurf1) and histone deacetylase 4 (HDAC4) mRNAs were inhibited by miR-10b-5p. The expression of neutral sphingomyelinase 2 (N-SMase2) was decreased in hypoxia ECFCs, and this result was consistent with the changes in miR-10b-5p in hyp-exo. CONCLUSIONS Due to a reduction of miR-10b-5p, which targets the fibrotic genes Smurf1 and HDAC4, the anti-fibrotic effects of hyp-exo were abolished.

We examined whether the inflammation resolution mediator lipoxin ALXACirculating LXAWe found that LXA

We evaluated the role of IL-10- in IL-33-mediated cholesterol reduction in macrophage-derived foam cells (MFCs) and the mechanism by which IL-33 upregulates IL-10. Serum IL-33 and IL-10 levels in coronary artery disease patients were measured. The effects of IL-33 on intra-MFC cholesterol level, IL-10, ABCA1 and CD36 expression, ERK 1/2, Sp1, STAT3 and STAT4 activation, and IL-10 promoter activity were determined. Core sequences were identified using bioinformatic analysis and site-specific mutagenesis. The serum IL-33 levels positively correlated with those of IL-10. IL-33 decreased cellular cholesterol level and upregulated IL-10 and ABCA1 but had no effect on CD36 expression. siRNA-IL-10 partially abolished cellular cholesterol reduction and ABCA1 elevation by IL-33 but did not reverse the decreased CD36 levels. IL-33 increased IL-10 mRNA production but had little effect on its stability. IL-33 induced ERK 1/2 phosphorylation and increased the luciferase expression driven by the IL-10 promoter, with the highest extent within the −2000 to −1752 bp segment of the 5′-flank of the transcription start site; these effects were counteracted by U0126. IL-33 activated Sp1, STAT3 and STAT4, but only the STAT3 binding site was predicted in the above segment. Site-directed mutagenesis of the predicted STAT3-binding sites (CTGCTTCCTGGCAGCAGAA→CTGCCTGGCAGCAGAA) reduced luciferase activity, and a STAT3 inhibitor blocked the regulatory effects of IL-33 on IL-10 expression. Chromatin immunoprecipitation (CHIP) confirmed the STAT3-binding sequences within the −1997 to −1700 and −1091 to −811 bp locus regions. IL-33 increased IL-10 expression in MFCs via activating ERK 1/2 and STAT3, which subsequently promoted IL-10 transcription and thus contributed to the beneficial effects of IL-33 on MFCs. A recently identified signaling protein may help prevent the accumulation of cholesterol in patients with cardiovascular disease. Although early studies suggest that interleukin-33 (IL-33) acts on the cholesterol-laden ‘foam cells’ that contribute to risk of heart attack and stroke, its function is poorly defined. After examining patients with coronary artery disease, researchers led by Nian-Sang Luo, Yang-Xin Chen and Jing-Feng Wang at China's Sun Yat-sen University, Guangzhou, found that IL-33 levels correlate with production of interleukin-10 (IL-10), another protein that regulates cholesterol. The researchers subsequently showed that IL-33 initiates a signaling cascade that fuels IL-10 expression, and that this in turn stimulates production of proteins that actively pump cholesterol out of foam cells. This pathway may therefore offer a clinically useful target for the management of cardiovascular disease.

Objectives Yes-associated protein (YAP) has been reported to regulate cell proliferation and differentiation. We aimed to characterize the role of YAP in angiotensin II (Ang II)-induced hypertensive vascular remodelling (HVR) and vascular smooth muscle cells (VSMCs) phenotypic modulation and to explore the underlying mechanisms. Materials and methods An HVR rat model was established by continuous Ang II infusion for 2 weeks. Western blotting, qRT-PCR, and confocal microscopy were conducted to assess YAP expression. YAP-shRNA interfering plasmid and adenovirus were constructed to knock down YAP. We used cell proliferation and migration assays, accompanied by pathway inhibitors, to evaluate the biological function and underlying mechanisms. Results Ang II upregulated YAP expression in the media of carotid artery; however, in vivo YAP silencing significantly mitigated HVR, independent of the blood pressure level. Ang II upregulated YAP expression and promoted YAP nuclear accumulation in a dose- and time-dependent manner in rat VSMCs. YAP knockdown ameliorated Ang II-induced VSMCs phenotypic modulation. The regulation of YAP by Ang II could be blocked by pretreatment with angiotensin receptor type 1 antagonist losartan or F-actin depolymerizing agent latrunculin B but not the AT2R antagonist PD 123319. Disrupting the YAP-TEA domain (TEAD) interaction with verteporfin inhibited Ang II-induced VSMCs phenotypic modulation. Conclusions Yes-associated protein mediated angiotensin II-induced VSMCs phenotypic modulation and vascular remodelling. YAP is a potential therapeutic target for HVR beyond blood pressure control.

Purpose Several studies have reported apparently conflicting findings for the effects of tumor necrosis factor-alpha ( TNF-α ) G-308A polymorphism on coronary heart disease (CHD) susceptibility. We undertook a systematic review and meta-analysis to investigate the association between this gene variant and CHD predisposition. Methods We systematically searched electronic databases (Medline, EMbase, Chinese BioMedical, BIOSIS, Global Health, PsycINFO, Allied and Complementary Medicine Database, Cochrane Library, HuGE Navigator, and British Nursing) for relevant studies published between 1947 and October, 2010. Summarized estimation of odds ratio (OR) and 95% confidence interval (CI) were calculated. Publication bias and heterogeneity among studies were explored. Results We identified 24 studies providing data for 9 921 cases and 7 944 controls. Pooled analysis based on ORs adjusted by CHD risk factors showed that carrying the TNF-α gene A variant conferred a 1.5-fold increased risk of developing CHD (AG+AA vs. GG, OR=1.50, 95% CI: 1.23-1.77) in Caucasian population. No significant association between the gene polymorphism and CHD risk could be found in other ethnic groups. Conclusions It is probable that carrying the A variant is associated with CHD risk in Caucasians but not in Asians, Indians, or Africans. Further studies are merited to assess the association in greater details, especially in Asians, Indians and Africans.