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Background: To investigate the relationship between red blood cell (RBC) folate and congestive heart failure (CHF). Methods: We extracted the concentrations of RBC folate and collated CHF information from the National Health and Nutrition Examination Survey (NHANES) survey (12820 individuals). Weighted univariate logistic regression, weighted multivariate logistic regression, and restrictive cubic spline (RCS) were used to assess the relationship between RBC folate concentrations and CHF. Results: The unadjusted model showed that the highest tertile group of RBC folate concentration was significantly associated with a higher risk of CHF compared to the lowest tertile group of RBC folate levels (odds ratio [OR] = 3.09; 95% confidence interval [CI], 2.14-4.46). Similar trends were seen in the multivariate-adjusted analysis (OR = 1.98; 95% CI: 1.27-3.09). The OR was > 1.0 when the predicted RBC folate exceeded 2757 nmol/L in the RCS model, indicating that the risk of CHF was low and relatively stable up to a predicted RBC folate level of 2757 nmol/L, but began to increase rapidly thereafter (p = 0.001). Conclusions: The risk of CHF may be increased either by high RBC folate concentrations (highest tertile of RBC folate or > 2637 nmol/L) or by folate deficiency. Considering the two sides of the association between RBC folate and CHF, there is a need for large-scale clinical research to better investigate if the association between RBC folate and CHF is a cause-effect relationship, what are the underlying pathophysiological basis, as well as to identify optimal dietary folate equivalent (DFE) and RBC folate concentration intervals.
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AIMS: Depression, the most prevalent psychiatric disorder, is associated with the occurrence and development of atrial fibrillation (AF). P2X7 receptor (P2X7R) activation participates in the development of depression, but little attention has been given to its role in AF. This study was to investigate the effects of P2X7R on AF in depression models. METHODS AND RESULTS: Lipopolysaccharide (LPS) and chronic unpredictable stress (CUS) were carried out to induce depression in rodents. Behavioural assessments, atrial electrophysiological parameters, electrocardiogram (ECG) parameters, western blot, and histology were performed. Atrial fibrillation inducibility was increased in both LPS- and CUS-induced depression, along with the up-regulation of P2X7R in atria. CUS facilitated atrial fibrosis. CUS reduced heart rate variability (HRV) and increased the expression of TH and GAP43, representing autonomic dysfunction. Down-regulation of Nav1.5, Cav1.2, Kv1.5, Kv4.3, Cx40, and Cx43 in CUS indicated the abnormalities in ion channels. In addition, the expression levels of TLR4, P65, P-P65, NLRP3, ASC, caspase-1, and IL-1ß were elevated in depression models. Pharmacological inhibitor (Brilliant Blue G, BBG) or genetic deficiency of P2X7R significantly mitigated depressive-like behaviours; ameliorated electrophysiological deterioration and autonomic dysfunction; improved ion channel expression and atrial fibrosis; and prevented atrial NLRP3 inflammasome activation in the pathophysiological process of AF in depression models. CONCLUSION: LPS or CUS induces AF and promotes P2X7R-dependent activation of NLRP3 inflammasome, whereas pharmacological P2X7R inhibition or P2X7R genetic deficiency prevents atrial remodelling without interrupting normal atrial physiological functions. Our results point to P2X7R as an important factor in the pathology of AF in depression.
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Fibrilação Atrial , Animais , Fibrilação Atrial/etiologia , Fibrilação Atrial/prevenção & controle , Depressão/prevenção & controle , Modelos Animais de Doenças , Fibrose , Inflamassomos/metabolismo , Lipopolissacarídeos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptores Purinérgicos P2X7/genética , Roedores/metabolismoRESUMO
OBJECTIVES: Serum matrix metalloproteinase (MMP) levels are associated with cardiovascular diseases. However, the causal associations between serum levels of specific MMPs and venous thromboembolism (VTE) remain unclear. The present study sought to explore the causal relationship between serum MMP levels and VTE by using the Mendelian randomization (MR) method. METHODS: In this study 2-sample MR study, the exposure data on serum MMP levels were derived from genome-wide association studies involving 21,758 individuals from 13 cohorts of European descent. The outcome data on VTE, including deep vein thrombosis and pulmonary embolism, were derived from the FinnGen research project. The primary method used was the inverse-variance weighting method. The MR-Egger intercept test and the Cochran Q test were used to evaluate pleiotropy and heterogeneity. RESULTS: Using the inverse-variance weighting method, higher serum MMP-12 levels were found to be associated with an increased risk of VTE (odds ratio, 1.04; 95% confidence interval, 1.01 to 1.07; p=0.001). Moreover, there was a weak association between the levels of certain MMPs and VTE. Sensitivity analyses revealed no significant heterogeneity and pleiotropy in our study, and the Steiger directionality test did not reveal a significant reverse causation association. CONCLUSIONS: There is a causal association between MMP-12 levels and VTE, which may have substantial implications for the diagnostic and therapeutic strategies used for VTE.
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Estudo de Associação Genômica Ampla , Metaloproteinases da Matriz , Análise da Randomização Mendeliana , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/sangue , Metaloproteinases da Matriz/sangue , Causalidade , Metaloproteinase 12 da Matriz/sangue , Metaloproteinase 12 da Matriz/genéticaRESUMO
Atrial fibrillation (AF) is common in pulmonary hypertension (PH), whereas the mechanisms and treatments remain to be explored. TRPV2 regulates the structure and function of the cardiovascular system; however, little attention has been given to its role in AF. This study was to determine whether TRPV2 was involved in PH-induced AF and the effects of TRPV2 inhibitor tranilast on AF in rat models of PH. Monocrotaline (MCT) and SU5416/hypoxia (SuHx)-induced PH models were performed to detect atrial electrophysiological parameters. Daily tranilast (a TRPV2 inhibitor) or saline was given starting 1 day before PH establishment. PH increased the susceptibility to AF, with TRPV2 up-regulated in the right atria. Compared to PH rats, tranilast reduced AF inducibility and the prolongations of ERP and APD; mitigated cardiopulmonary remodeling and the increases in P-wave duration and P-R interval; partially reversed the down-regulation of ion channels such as Cav1.2, Nav1.5, Kv4.3, Kv4.2, Kv1.5, Kir2.1, Kir3.1, Kir3.4 as well as connexin (Cx) 40 and Cx43; improved right atrial (RA) fibrosis, enlargement, and myocardial hypertrophy; decreased the accumulation of inflammatory cells; down-regulated inflammatory indicators such as TNF-α, IL-1ß, CXCL1, and CXCL2; and inhibited the activation of the PI3K-AKT-NF-κB signaling pathway. Our results reveal that TRPV2 participates in PH-induced AF, and TRPV2 inhibitor tranilast prevents PH-induced RA remodeling. TRPV2 might be a promising target for PH-induced AF.
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Fibrilação Atrial , Hipertensão Pulmonar , ortoaminobenzoatos , Ratos , Animais , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/metabolismo , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Átrios do Coração/metabolismo , Modelos Animais de DoençasRESUMO
BACKGROUND: Post-operative atrial fibrillation (POAF) is a common complication in patients undergoing cardiac surgery. The purinergic receptor P2X7 (P2X7R) is involved in some cardiovascular diseases, whereas its effects on atrial fibrillation (AF) are unclear. OBJECTIVE: This study was to assess the effect of P2X7R on atrial arrhythmogenic remodeling in the rat model of sterile pericarditis (SP). METHODS: Male Sprague-Dawley (SD) rats were used to induce the SP model. Electrocardiogram, atrial electrophysiological protocol, histology, mRNA sequencing, real-time quantitative PCR, western blot, and Elisa assay were performed. RESULTS: SP significantly up-regulated P2X7R expression; increased AF susceptibility; reduced the protein expression of ion channels including Nav1.5, Cav1.2, Kv4.2, Kv4.3, and Kv1.5; caused atrial fibrosis; increased norepinephrine (NE) level in plasma; promoted the production of inflammatory cytokines such as TNF-α, IL-1ß, and IL-6; increased the accumulation of immune cells (CD68- and MPO- positive cells); and activated NLRP3 inflammasome signaling pathway. P2X7R antagonist Brilliant Blue G (BBG) mitigated SP-induced alterations. The mRNA sequencing demonstrated that BBG prevented POAF mainly by regulating the immune system. In addition, another selective P2X7R antagonist A740003, and IL-1R antagonist anakinra also reduced AF inducibility in the SP model. CONCLUSIONS: P2X7R inhibition prevents SP-induced atrial proarrhythmic remodeling, which is closely associated with the improvement of inflammatory changes, ion channel expression, atrial fibrosis, and sympathetic activation. The findings point to P2X7R inhibition as a promising target for AF (particularly POAF) and perhaps other conditions.
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Fibrilação Atrial , Pericardite , Humanos , Ratos , Masculino , Animais , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/etiologia , Fibrilação Atrial/prevenção & controle , Ratos Sprague-Dawley , Receptores Purinérgicos P2X7/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fibrose , RNA MensageiroRESUMO
The axial force transfer ratio of steel-concrete joints in hybrid box girder bridges is crucial for bridge design. However, the current standard oversimplifies the transfer ratio distribution coefficients, and both model tests and finite element analysis are time- and labor-intensive. This article proposes a simplified calculation model based on the deformation coordination theory to estimate the transfer ratio of the axial force between the bearing plate and shear connectors of the steel-concrete joint under compression bending conditions. Additionally, a large-scale model (1/5 scale) is established, and the mechanical properties of the steel-concrete joint section under compression-bending conditions are experimentally tested. A three-dimensional finite element model is developed and verified using the obtained test data. Results confirm the favorable mechanical properties and ample safety reserve of the SCJ, with all components remaining within the elastic stage under 1.6 times design conditions. By comparing the axial force transfer ratios obtained from the simplified calculation model and the finite element model, a small difference is observed, validating the reliability of the simplified calculation model. This paper provides a straightforward and efficient method for the design and evaluation of steel-concrete joints in hybrid box girder bridges.
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Background: Reports show that the left ventricular myocardial work index (LVMWI) is a novel parameter for evaluating cardiac function. Decompensated heart failure leads to a high rate of early mortality in advanced patients with light-chain cardiac amyloidosis (AL-CA) and prevents them from a relatively delayed response to chemotherapy. This study aimed to assess the association of the LVMWI with short-term outcomes and to construct a simple model for risk stratification. Methods: A total of 79 patients with an initial diagnosis of AL-CA were included in this retrospective cohort study. LVMWI was calculated by integrating brachial artery cuff blood pressure and left ventricular longitudinal strain (LVLS). The short-term outcome was defined as 6-month all-cause mortality. Receiver operating characteristic (ROC), logistic regression, and Kaplan-Meier analysis were used in this study. Results: The median follow-up time was 21 months (3-36 months), and 23 (29%) patients died in the first 6 months. The time-dependent ROC and the area under the curve (AUC) showed that the LVMWI had the best predictive potential at the 6-month time point [AUC =0.805; 95% confidence interval (CI): 0.690-0.920]. A bivariate prognostic model based on the LVMWI was constructed, and D-dimer showed a synergistic effect with optimum predicted potential (AUC =0.877; 95% CI: 0.791-0.964). Kaplan-Meier analysis demonstrated that patients with two, one, and none of the variates beyond the cut-off value bore a different risk of 6-month all-cause mortality (accumulated mortality was 86%, 30%, 3%, respectively; log-rank, P<0.001). Multivariate nested logistic regression showed that the level of D-dimer provided an incremental prognostic value (Δχ2=10.3; P=0.001) to the value determined from New York Heart Association (NYHA) classification and the LVMWI. Conclusions: The LVMWI is associated with the short-term outcome of patients with AL-CA. The D-dimer test provides additional prognostic information for the LVMWI.
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BACKGROUND: Amyloid light-chain cardiac amyloidosis (AL-CA) patients experiencing RV failure have a poorer prognosis. The echocardiographic ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary arterial systolic pressure (PASP) serves as a non-invasive proxy for evaluating the coupling between the right ventricle (RV) and pulmonary circulation. The aim of this study was to assess the association between the TAPSE/PASP ratio and short-term outcome in patients with AL-CA. METHODS: Seventy-one patients diagnosed with AL-CA were enrolled in this retrospective cohort study.Short-term outcome was defined as 6-month all-cause mortality. Receiver operating characteristic (ROC), logistic regression, and Kaplan-Meier analysis were used in this study. RESULTS: Among seventy-one patients with AL-CA (mean age, 62 ± 8 years, 69% male), 17 (24%) died within the first 6 months (mean follow-up period 55 ± 48 days). Linear regression analysis indicated that the TAPSE/PASP ratio was correlated with RV global longitudinal strain (r = -0.655, p < 0.001), RV free wall thickness (r = -0.599, p < 0.001), and left atrial reservoir strain (r = 0.770, p < 0.001). The time-dependent ROC and the area under the curve (AUC) showed that the TAPSE/PASP ratio was a better predictor (AUC = 0.798; 95% confidence interval (CI): 0.677-0.929) of short-term outcome than TAPSE (AUC = 0.734; 95% CI: 0.585-0.882) and PASP (AUC: 0.730; 95% CI: 0.587-0.874). Multivariate logistic regression showed that patients with the worse TAPSE/PASP (< 0.47 mm/mmHg) and lower systolic blood pressure (< 100 mmHg) had the highest risk of dying. CONCLUSIONS: The TAPSE/PASP ratio is associated with the short-term outcome of patients with AL-CA. The combination of TAPSE/PASP ratio < 0.474 mmHg and SBP < 100 mmHg could identify the subgroup of patients with AL-CA at elevated risk of poor prognosis.
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Amiloidose , Disfunção Ventricular Direita , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Estudos Retrospectivos , Ecocardiografia Doppler , Estudos Prospectivos , Pressão Sanguínea/fisiologia , Amiloidose/diagnóstico por imagem , Função Ventricular Direita/fisiologia , PrognósticoRESUMO
BACKGROUND: Light-chain (AL) cardiorenal amyloidosis has been characterized as type 5 cardiorenal syndrome with fluid overload and poor prognosis. Cancer antigen 125 (CA125) has the potential for use in evaluating fluid load and prognosis for heart failure. However, less details for CA125 in AL cardiorenal amyloidosis have been reported. METHODS: Sixty patients diagnosed with AL cardiorenal amyloidosis were enrolled in this retrospective study. Patients were divided into two groups according to the cutoff point of CA125 level (35 U/mL). Logistic regression was used to screen variables associated with CA125. Cox regression analyses was utilized to verify the prognostic potential of CA125. RESULTS: The mean age was 61±8 years, and 68% of the participants were male. Compared to patients with normal CA125 levels (≤35 U/mL), patients with high levels of CA125 (>35 U/mL) had a higher proportion of New York Heart Association class >II, pericardial effusion, and edema, as well as a lower level of albumin and left ventricular longitudinal strain (LVLS). Logistic regression showed age, albumin, and LVLS to be independently associated with CA125. Seventeen (28%) patients died during the follow-up. Multivariate model including CA125, estimated glomerular filtration rate, E/e' and left ventricular ejection fraction showed acceptable prognostic potential (C-index= 0.829, 95%CI 0.749 to 0.909). CA125 remained an independent prognostic factor (HR=1.018, 95%CI 1.005 to 1.031, P=0.008) after adjusting for the remaining three variates and provided a significant incremental effect to the risk determined from them (C-index 0.829 vs 0.784, P=0.037). CONCLUSIONS: Serum CA125 level was associated with long-term prognosis of AL cardiorenal amyloidosis.
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BACKGROUND: Atrial fibrillation (AF) is one of the most prevalent sustained cardiac arrhythmias. The latest studies have revealed a tight correlation between nonalcoholic fatty liver disease (NAFLD) and AF. However, the exact molecular mechanisms underlying the association between NAFLD and AF remain unclear. The current research aimed to expound the genes and signaling pathways that are related to the mechanisms underlying the association between these two diseases. MATERIALS AND METHODS: NAFLD- and AF- related differentially expressed genes (DEGs) were identified via bioinformatic analysis of the Gene Expression Omnibus (GEO) datasets GSE63067 and GSE79768, respectively. Further enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), the construction of a protein-protein interaction (PPI) network, the identification of significant hub genes, and receiver operator characteristic curve analysis were conducted. The gene-disease interactions were analyzed using the Comparative Toxicogenomics Database. In addition, the hub genes were validated by quantitative Real-Time PCR (qRT-PCR) in NAFLD cell model. RESULTS: A total of 45 co-expressed differentially expressed genes (co-DEGs) were identified between the NAFLD/AF and healthy control individuals. GO and KEGG pathway analyses revealed that the co-DEGs were mostly enriched in neutrophil activation involved in the immune response and cytokine-cytokine receptor interactions. Moreover, eight hub genes were selected owing to their high degree of connectivity and upregulation in both the NAFLD and AF datasets. These genes included CCR2, PTPRC, CXCR2, MNDA, S100A9, NCF2, S100A12, and S100A8. CONCLUSIONS: In summary, we conducted the gene differential expression analysis, functional enrichment analysis, and PPI analysis of DEGs in AF and NAFLD, which provides novel insights into the identification of potential biomarkers and valuable therapeutic leads for AF and NAFLD.