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Background: This study investigated factors influencing discrepancies between fractional flow reserve (FFR) and resting full-cycle ratio (RFR) in the functional assessment of coronary artery stenosis in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Methods: We included 320 diseased vessels from 253 consecutive patients with NSTE-ACS. Vessels were categorized into four groups based on FFR ≤ 0.80 and RFR ≤ 0.89 thresholds: group 1 concordant negative (RFR-/FFR-), group 2 positive RFR and negative FFR (RFR+/FFR-), group 3 negative RFR and positive FFR (RFR-/FFR+), and group 4 concordant positive (RFR+/FFR+). Univariate and multivariate logistic regression analyses were conducted to identify predictors of diagnostic discrepancy between FFR and RFR. Results: Of the 320 diseased vessels, 182 (56.9%) were in group 1 (RFR-/FFR-), 33 (10.3%) in group 2 (RFR+/FFR-), 31 (9.7%) in group 3 (RFR-/FFR+), and 74 (23.1%) in group 4 (RFR+/FFR+). The concordance between FFR and RFR was 80.0%. Notably, left anterior descending artery (LAD) lesions exhibited significantly lower consistency compared to non-LAD lesions (p = 0.001), with distinct differences in FFR and RFR values between these groups (p < 0.001). The presence of a LAD lesion emerged as an independent predictor of diagnostic inconsistency between positive RFR and negative FFR measurements (p = 0.001). Conclusions: LAD involvement independently predicts diagnostic discrepancies between FFR and RFR in evaluating functional coronary artery stenosis in NSTE-ACS patients.
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Background: The SYNTAX score (SS) is useful for predicting clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). The clinical SYNTAX score (CSS), developed by combining clinical parameters with the SS, enhances the risk model's ability to predict clinical outcomes. However, prior research has not yet evaluated the prognostic capacity of CSS in patients with complex coronary artery disease (CAD) and chronic renal insufficiency (CRI) who are undergoing PCI. We aimed to demonstrate the prognostic potential of CSS in assessing long-term adverse events in this high-risk patient cohort. Methods: A total of 962 patients with left main and/or three-vessel CAD and CRI were enrolled in the study spanning from January 2014 to September 2017. The CSS was calculated by multiplying the SS by the modified age, creatinine, and left ventricular ejection fraction (ACEF) score (age/ejection fraction + 1 for each 10 mL of creatinine clearance < 60 mL/min per 1.73 m 2 ). The patients were categorized into three groups based on their CSS values: low-CSS group (CSS < 18.0, n = 321), mid-CSS group (18.0 ≤ CSS < 28.3, n = 317), and high-CSS group (CSS ≥ 28.3, n = 324) as per the tertiles of CSS. The primary endpoints were all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints included myocardial infarction (MI), unplanned revascularization, stroke, and major adverse cardiac and cerebrovascular events (MACCE). Results: At the median 3-year follow-up, the high-CSS group exhibited higher rates of ACM (19.4% vs. 6.6% vs. 3.6%, p < 0.001), CM (15.6% vs. 5.1% vs. 3.2%, p = 0.003), and MACCE (33.8% vs. 29.0% vs. 20.0%, p = 0.005) in comparison to the low and mid-CSS groups. Multivariable Cox regression analysis revealed that CSS was an independent predictor for all primary and secondary endpoints (p < 0 .05). Moreover, the C-statistics of CSS for ACM (0.666 vs. 0.597, p = 0.021) and CM (0.668 vs. 0.592, p = 0.039) were significantly higher than those of SS. Conclusions: The clinical SYNTAX score substantially enhanced the prediction of median 3-year ACM and CM in comparison with SS in complex CAD and CRI patients following PCI.
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A sandwich-structured composite nanoenzyme (NH2-MIL-101(Fe)@Au@MIP) was prepared using molecularly imprinted polymers, metal-organic frameworks, and gold nanoparticles and a highly selective glutathione (GSH) colorimetric sensor was constructed. The inner part of the composite nanoenzymes is a metal-organic framework loaded with gold nanoparticles (AuNPs), NH2-MIL-101(Fe)@Au, which has superior peroxidase-like activity compared with NH2-MIL-101(Fe). This is due to the surface plasmon resonance effect of AuNPs. GSH can form strong Au-S bonds with AuNPs, which can significantly reduce the enzymatic activity of NH2-MIL-101(Fe)@Au, thereby changing the absorbance at 450 nm of the sensing system. The degree of change in absorbance is correlated with the concentration of GSH. In the outer part, the molecularly imprinted polymer with oxidized glutathione (GSSG) as a dummy template provided specific pores, which significantly improved the selectivity of the sensing system. The sensor showed good GSH sensing performance in the range 1 ~ 50 µM with a lower limit of detection (LOD) of 0.231 µM and good sensing performance in fetal bovine serum, indicating its high potential for clinical diagnostic applications.
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Nanopartículas Metálicas , Estruturas Metalorgânicas , Estruturas Metalorgânicas/química , Ouro/química , Colorimetria , Nanopartículas Metálicas/química , GlutationaRESUMO
BACKGROUND: The SYNTAX score â ¡ 2020 (SSâ ¡-2020) was created as a customized decision-making tool for individuals diagnosed with complex coronary artery disease (CAD). Nevertheless, there has been a scarcity of research investigating the long-term predictive significance of SSâ ¡-2020 for patients with both CAD and chronic renal insufficiency (CRI) who undergo percutaneous coronary intervention (PCI). AIMS: We sought to showcase the prognostic capacity of SSII-2020 in evaluating long-term all-cause mortality (ACM) within this high-risk patient cohort. METHODS: A retrospective cohort comprising 1156 individuals diagnosed with CRI and exhibiting left main CAD, three-vessel CAD or both was included in this investigation. We categorized participants into three groups based on the optimal SSII-2020 threshold for predicting long-term ACM, determined using the X-tile software. RESULTS: At the median follow-up duration of 6.3 years, the ACM rates were determined to be 10% in the low, 17% in the moderate, and 28% in the high SSII-2020 groups (p < 0.001). Employing multivariate Cox regression analysis, it was observed that the high SSII-2020 group exhibited a 3.289-fold increased risk of ACM (95% confidence interval [CI]: 2.229-4.856, p < 0.001) compared with the low SSII-2020 group, whereas the high SSII-2020 group displayed a 1.757-fold (95% CI: 1.190-2.597, p = 0.005) in comparison to the median SSII-2020 groups. Compared with SSII, the SSII-2020 had an incremental value for predicting 7-year ACM (C-index: 0.662 vs. 0.534, p = 0.007; IDI: 0.016, p < 0.001). CONCLUSIONS: SSII-2020 enhances long-term ACM prediction, facilitates improved risk stratification, and improves clinical utility for PCI patients with complex CAD and CRI.
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Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Insuficiência Renal Crônica , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Fatores de Risco , Medição de RiscoRESUMO
AIMS: Acute myocardial infarction (MI) causes inflammation, collagen deposition, and reparative fibrosis in response to myocyte death and, subsequently, a pathological myocardial remodelling process characterized by excessive interstitial fibrosis, driving heart failure (HF). Nonetheless, how or when to limit excessive fibrosis for therapeutic purposes remains uncertain. Galectin-3, a major mediator of organ fibrosis, promotes cardiac fibrosis and remodelling. We performed a preclinical assessment of a protein inhibitor of galectin-3 (its C-terminal domain, Gal-3C) to limit excessive fibrosis resulting from MI and prevent ventricular enlargement and HF. METHODS AND RESULTS: Gal-3C was produced by enzymatic cleavage of full-length galectin-3 or by direct expression of the truncated form in Escherichia coli. Gal-3C was intravenously administered for 7 days in acute MI models of young and aged rats, starting either pre-MI or 4 days post-MI. Echocardiography, haemodynamics, histology, and molecular and cellular analyses were performed to assess post-MI cardiac functionality and pathological fibrotic progression. Gal-3C profoundly benefitted left ventricular ejection fraction, end-systolic and end-diastolic volumes, haemodynamic parameters, infarct scar size, and interstitial fibrosis, with better therapeutic efficacy than losartan and spironolactone monotherapies over the 56-day study. Gal-3C therapy in post-MI aged rats substantially improved pump function and attenuated ventricular dilation, preventing progressive HF. Gal-3C in vitro treatment of M2-polarized macrophage-like cells reduced their M2-phenotypic expression of arginase-1 and interleukin-10. Gal-3C inhibited M2 polarization of cardiac macrophages during reparative response post-MI. Gal-3C impeded progressive fibrosis post-MI by down-regulating galectin-3-mediated profibrotic signalling cascades including a reduction in endogenous arginase-1 and inducible nitric oxide synthase (iNOS). CONCLUSION: Gal-3C treatment improved long-term cardiac function post-MI by reduction in the wound-healing response, and inhibition of inflammatory fibrogenic signalling to avert an augmentation of fibrosis in the periinfarct region. Thus, Gal-3C treatment prevented the infarcted heart from extensive fibrosis that accelerates the development of HF, providing a potential targeted therapy.
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Cardiomiopatias , Galectina 3 , Infarto do Miocárdio , Miocárdio , Animais , Ratos , Arginase/metabolismo , Cardiomiopatias/metabolismo , Fibrose , Galectina 3/antagonistas & inibidores , Infarto do Miocárdio/patologia , Miocárdio/patologia , Volume Sistólico , Função Ventricular Esquerda , Remodelação Ventricular/fisiologiaRESUMO
Objective: To determine whether the inclusion of white blood cell (WBC) counts in the SYNTAX score (SS) or SS II models could improve the models' performance for risk stratification in individuals with chronic renal insufficiency (CRI) following percutaneous coronary intervention (PCI). Methods: In total, 2,313 patients with CRI, who were subjected to PCI and had data available on in-hospital WBC (ih-WBC) counts, were recruited. Patients were divided into 3 groups as per their ih-WBC counts (low, medium, and high). The primary endpoints were all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints incorporated myocardial infarction, stroke, unplanned revascularization, and major adverse cardiovascular and cerebrovascular events (MACCEs). Results: During a median follow-up of 3 years, the high WBC group had the highest incidences of CM (2.4% vs. 2.1% vs. 6.7%; p < 0.001), ACM (6.3% vs. 4.1% vs. 8.2%; p < 0.001), unplanned revascularization (8.4% vs. 12.4% vs. 14.1%; p < 0.001), and MACCEs (19.3% vs. 23.0% vs. 29.2%; p < 0.001) among the three groups. Multivariable Cox regression analysis depicted that the risk of ACM and CM in the high WBC group was 2.577 (95% confidence interval [CI]: 1.504-4.415, p < 0.001) and 3.850 (95% CI: 1.835-8.080, p < 0.001) times that in the low WBC group after adjusting for other confounding factors. A combination of ih-WBC counts with SS or SS II significantly improved the risk assessment and prediction of ACM and CM. Conclusion: The ih-WBC counts was associated with the risk of occurrence of ACM, CM, unplanned revascularization, and MACCEs in individuals with CRI following PCI. It provides an incremental predictive value for the occurrence of ACM and CM when included in SS or SS II models.
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Objective: The study aimed to assess the correlation and agreement between resting full-cycle ratio (RFR) and fractional flow reserve (FFR), and evaluate the guiding value of a hybrid RFR-FFR strategy for percutaneous coronary intervention (PCI) in a Chinese real-world cohort with non-ST elevation acute coronary syndrome (NSTE-ACS). Materials and methods: A total of 109 patients with NSTE-ACS (149 diseased vessels), who underwent an invasive physiological assessment in Cangzhou Central Hospital, Hebei Medical University, were prospectively enrolled from September 2021 to May 2022. FFR ≤ 0.80 was used as the gold standard for coronary artery functional ischemia. We utilized the Pearson correlation and Bland-Altman analysis to assess the correlation and agreement between RFR and FFR. The diagnostic value of RFR predicting FFR ≤ 0.80 was evaluated in accordance with the receiver operating characteristic (ROC) curve. The hybrid RFR-FFR strategy, which was established according to determining the "gray zone" of RFR (FFR was further assessed using vasodilators only for diseased vessels in the "gray zone"), needed to afford over 95% global agreement with the FFR-only strategy. Results: Resting full-cycle ratio was significantly linearly linked with FFR (R 2 = 0.636, P < 0.001). The accuracy, specificity, and sensitivity for RFR ≤ 0.89 predicting FFR ≤ 0.80 were 81.2, 70.8, and 86.1%, respectively. The area under the ROC curve for RFR predicting FFR ≤ 0.80 was 0.881 (P < 0.001), and the cutoff value was 0.90. The "gray zone" of RFR was 0.85-0.93. The positive and negative predictive values of the hybrid RFR-FFR strategy were 0.95 and 0.93, respectively. The hybrid RFR-FFR strategy exhibited an agreement of 96.0% with FFR and obviated the need for a vasodilator by 60.4%. Conclusion: Resting full-cycle ratio and FFR have high correlation and consistency. The hybrid RFR-FFR strategy highlights considerably enhanced agreement with the FFR-only strategy, whilst making the requirement of vasodilator administration less than a half.
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Background: The residual SYNTAX score (RSS) is considered a powerful prognostic indicator for determining a reasonable revascularization strategy in patients undergoing percutaneous coronary intervention (PCI), but the absence of clinical parameters is one of the limitations of RSS, especially in the chronic renal insufficiency (CRI) comorbidity setting. The present work aimed to investigate the incremental prognostic value of clinical residual SYNTAX score (CRSS) compared with RSS in CRI cases after PCI. Methods: Totally 2,468 consecutive CRI cases who underwent PCI from January 2014 to September 2017 were included in this retrospective analysis. CRSS was obtained by multiplying RSS by the modified ACEF score. Individuals with CRSS >0 were considered to have incomplete revascularization and stratified by CRSS tertiles, the remaining cases constituted the complete revascularization (CR) group. The outcomes between these groups were compared. Results: At a median follow-up of 3 years, compared with CR group, individuals with CRSS >12 showed elevated rates of all clinical outcomes, and those with CRSS ≤ 12 showed similar all-cause and cardiac mortality rates. In multivariable analysis, CRSS was a powerful independent predictive factor of all clinical outcomes. The net reclassification improvement levels of CRSS over RSS for all-cause and cardiac mortality rates were 10.3% (p = 0.007) and 16.4% (p < 0.001), respectively. Compared with RSS, CRSS markedly ameliorated all-cause and cardiac mortality risk stratification. Conclusions: Compared with RSS, CRSS has incremental predictability for long-term all-cause and cardiac mortality in CRI cases following PCI.
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This paper was originally published in Aging Advance Online Publications on February 26, 2021. In compliance with Aging's withdrawal policy, the paper was withdrawn in its entirety. It will not appear in Aging internal or any external indexes or archives.
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Objective: Advancing age is a major risk factor of atherosclerosis (AS). Nevertheless, the mechanism underlying this phenomenon remains indistinct. Herein, this study conducted a comprehensive analysis of the biological implications of aging-related genes in AS. Methods: Gene expression profiles of AS and non-AS samples were curated from the GEO project. Differential expression analysis was adopted for screening AS-specific aging-related genes. LASSO regression analysis was presented for constructing a diagnostic model, and the discriminatory capacity was evaluated with ROC curves. Through consensus clustering analysis, aging-based molecular subtypes were conducted. Immune levels were estimated based on the expression of HLAs, immune checkpoints, and immune cell infiltrations. Key genes were then identified via WGCNA. The effects of CEBPB knockdown on macrophage polarization were examined with western blotting and ELISA. Furthermore, macrophages were exposed to 100 mg/L ox-LDL for 48 h to induce macrophage foam cells. After silencing CEBPB, markers of cholesterol uptake, esterification and hydrolysis, and efflux were detected with western blotting. Results: This study identified 28 AS-specific aging-related genes. The aging-related gene signature was developed, which could accurately diagnose AS in both the GSE20129 (AUC = 0.898) and GSE43292 (AUC = 0.685) datasets. Based on the expression profiling of AS-specific aging-related genes, two molecular subtypes were clustered, and with diverse immune infiltration features. The molecular subtype-relevant genes were obtained with WGCNA, which were markedly associated with immune activation. Silencing CEBPB triggered anti-inflammatory M2-like polarization and suppressed foam cell formation. Conclusion: Our findings suggest the critical implications of aging-related genes in diagnosing AS and modulating immune infiltrations.
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AIMS: This study investigated the association of circulating ceramides in patients with comorbid acute coronary syndrome and type 2 diabetes mellitus (ACS-DM). METHODS: A total of 761 patients with coronary heart disease who were admitted to the Department of Cardiology at the Chinese PLA General Hospital from March to August 2018 were enrolled in this study. Of these 761 patients, 282 were diagnosed with acute coronary syndrome (ACS). We selected 65 patients with ACS-DM (ACS-DM group; mean age 64.88 years; 38 men) and 65 patients with ACS but without any comorbidities (ACS group; mean age 64.68 years; 38 men); the two groups were matched by age and sex. We determined four circulating ceramides in 130 plasma samples: Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:1), and Cer(d18:1/24:0). The ceramides in plasma samples from patients with ACS and those from patients with ACS-DM were compared. Pearson correlation coefficients between individual ceramides and traditional cardiovascular risk factors for the whole study population were calculated. Multiple logistic regression models were used to evaluate the relativity between the ceramide and ACS-DM. RESULTS: Compared with the ACS group, the levels of Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1) and their ratios to Cer(d18:1/24:0) were higher in the ACS-DM group and Cer(d18:1/24:0) was lower in the ACS-DM group (P < 0.05). Correlation analysis demonstrated mild-to-moderate correlations of ceramide and traditional cardiovascular risk factors. There were relatively strong correlations of Cer(d18:1/18:0) and Cer(d18:1/24:1) with C-reactive protein, blood lipids, fasting blood glucose, and glycated hemoglobin A1c. In multiple logistic regression models, Cer(d18:1/18:0) [odds ratio (OR) 2.396; 95% confidence interval (CI) 1.103-5.205; P = 0.027], Cer(d18:1/24:1) (OR 2.826; 95% CI 1.158-6.896; P = 0.023), Cer(d18:1/18:0)/Cer(d18:1/24:0) (OR 2.242; 95% CI 1.103-4.555; P = 0.026), and Cer(d18:1/24:1)/Cer(d18:1/24:0) (OR 2.673; 95% CI 1.225-5.836; P = 0.014) were positively correlated with ACS-DM, and Cer(d18:1/24:0) (OR 0.200; 95% CI 0.051-0.778; P = 0.020) was negatively correlated with ACS-DM. CONCLUSION: Circulating ceramides are positively correlated with the risk of ACS-DM comorbidity. These results give a new insight into the pathogenesis of ACS-DM comorbidity and could provide new options for risk estimation.
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OBJECTIVES: This study demonstrated the prognostic value of the residual SYNTAX score (rSS) for patients with chronic renal insufficiency (CRI). BACKGROUND: The rSS has been proposed as a useful tool for quantifying and stratifying the degree and complexity of residual stenosis and predicting long-term clinical outcomes following percutaneous coronary intervention (PCI). However, it has never been validated for patients with CRI. METHODS: A total of 2,468 consecutive patients with an estimated glomerular filtration rate <90 ml/min/1.73 m2 who underwent PCI were retrospectively enrolled. Patients with rSS >0 were defined as having incomplete revascularization and were stratified into the reasonable incomplete revascularization (RICR; 0 < rSS ≤ 8) group or the incomplete revascularization (ICR; rSS >8) group. Their outcomes were compared to those of the complete revascularization (CR) group. RESULTS: During follow-up (median, 3 years; range, 1.5-5 years), the ICR group had the highest incidence of all-cause death, cardiac death, myocardial infarction (MI), unplanned revascularization, stroke, and major adverse cardiovascular and cerebrovascular events (MACCE). Despite having higher rates of unplanned revascularization and MACCE, RICR group had comparable all-cause mortality, cardiac mortality, MI, and stroke with CR group. A multivariable Cox analysis indicated that rSS was an independent predictor of cardiac death, MI, unplanned revascularization, stroke, and MACCE. Furthermore, compared with baseline SYNTAX score, rSS had stronger prognostic accuracy when predicting the risk of unplanned revascularization, stroke, and MACCE at the 3-year follow-up. CONCLUSIONS: The rSS is a powerful indicator of clinical outcomes and may help determine reasonable levels of revascularization for patients with CRI following PCI.
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Doença da Artéria Coronariana/terapia , Técnicas de Apoio para a Decisão , Taxa de Filtração Glomerular , Indicadores Básicos de Saúde , Rim/fisiopatologia , Intervenção Coronária Percutânea , Insuficiência Renal Crônica/fisiopatologia , Idoso , Algoritmos , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Valor Preditivo dos Testes , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
AIMS: To examine the relationship of non-high-density lipoprotein cholesterol (non-HDL-C) level with cardiovascular disease (CVD) risk in type 2 diabetes patients and the general population by conducting a meta-analysis. METHODS: We made a comprehensive literature search for relevant observational studies investigating the relationship of non-HDL-C level with CVD risk in the general population and type 2 diabetes patients using the PubMed and Embase databases. Pooled risk ratio (RR) with 95% confidence intervals (CI) was calculated for the highest versus the reference lower non-HDL-Cl. RESULTS: A total of 13 studies with 156,381 individuals were included. The pooled RR of CVD was 1.59 (95% CI 1.46-1.72) in the general population and 1.99 (95% CI 1.57-2.51) in type 2 diabetes patients. Subgroup analysis showed the similar effect of non-HDL-C on CVD risk between men (RR1.98; 95% CI 1.70-2.30) and women (RR 1.63; 95% CI 1.35-1.96). However, elevated non-HDL-C was not associated with higher risk of cardiovascular mortality in the general population (RR 1.64; 95% CI 0.96-2.80) and type 2 diabetes patients (RR 1.08; 95% CI 0.57-2.07). CONCLUSIONS: Elevated non-HDL-C level is associated with an increased risk of CVD in the general population and type 2 diabetes patients.
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Doenças Cardiovasculares/diagnóstico , Colesterol/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Lipoproteínas/efeitos adversos , Doenças Cardiovasculares/patologia , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Masculino , Fatores de RiscoRESUMO
Association of early menopause with increased risk of cardiovascular events has been confirmed in previous studies. SYNTAX score (SX-score) can comprehensively quantify severity of coronary artery disease (CAD) and predict the outcomes of patients with CAD. However, the association of early menopause with SX-score has never been reported.We prospectively included 1875 consecutive postmenopausal patients who underwent coronary angiography (CAG) and were angiographically diagnosed with CAD from January 2011 to December 2013. SX-score was calculated using the SX-score algorithm based on diagnostic angiogram. Ordinal logistic regression analysis was used to investigate the association between early menopause and SX-score.Patients with early menopause were more likely to have a history of hypertension, diabetes, hyperlipidemia, and less likely to smoking. Besides, they have higher fasting glucose, hemoglobin A1C (HbA1c), total cholesterol (TC), low-density lipoprotein (LDL), triglyceride (TG), and body mass index (BMI) compared with the patients without early menopause. Moreover, patients with early menopause have higher SX-score and multi-vessel diseases. Ordinal logistic regression analysis showed that age, hypertension, diabetes, and early menopause exerted independent influences on SX-score. The patients undergone oophorectomy, early menopause was highly associated with SX-score.Early menopause was an independent predictor of SX-score in postmenopausal patients with CAD.
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Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Menopausa , Adulto , Idoso , Algoritmos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de RiscoRESUMO
The present study aimed to investigate the expression of microRNA (miR)133a in patients with or without acute myocardial infarction (AMI) following radical surgery for gastric cancer, and to explore its underlying mechanisms. Blood samples were collected from patients with or without AMI in order to detect the expression levels of miR133a and endothelial injury markers. In addition, an AMI rat model was established. Reverse transcriptionquantitative polymerase chain reaction was used to detect the mRNA expression levels of miR133a and Bcell lymphoma 2like 1 (Bcl2l1). In addition, an ELISA assay was used for endothelial injury marker analysis. To investigate the effects of miR133a on human umbilical vein endothelial cells (HUVECs), a miR133a inhibitor was used. Cell proliferation and apoptosis were subsequently detected using an MTT assay and ï¬ow cytometry. Western blot analysis was also conducted to detect Bcl2l1 protein expression. The results suggested that patients with AMI exhibited significantly increased expression of endothelial injury markers (von Willebrand factor, hearttype fatty acidbinding protein and cardiac troponin I) and miR133a in blood samples compared with patients without AMI. In addition, treatment with a miR133a mimic was able to upregulate the expression of endothelial injury markers in an AMI rat model, whereas treatment with a miR133a inhibitor had the opposite effect. Furthermore, cellular experiments indicated that a miR133a inhibitor could promote HUVEC proliferation and reduce cell apoptosis. The present results also confirmed that miR133a directly targets Bcl2l1 and negatively regulates Bcl2l1 expression. In conclusion, the results of the present study suggested that miR133a was involved in the endothelial injury process after AMI by targeting Bcl2l1.
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Regulação da Expressão Gênica , MicroRNAs/genética , Infarto do Miocárdio/etiologia , Neoplasias Gástricas/complicações , Idoso , Animais , Apoptose/genética , Biomarcadores , Proliferação de Células , Modelos Animais de Doenças , Células Endoteliais da Veia Umbilical Humana , Humanos , Pessoa de Meia-Idade , Infarto do Miocárdio/metabolismo , Interferência de RNA , Ratos , Neoplasias Gástricas/cirurgia , Proteína bcl-X/genética , Proteína bcl-X/metabolismoRESUMO
The present study investigated the effects of micro (mi)RNA145 on acute myocardial infarction (AMI) and the potential underlying mechanism. A total of 6 AMI and 6 normal rat tissues were investigated for the present study. It was demonstrated that miRNA145 expression was downregulated in the AMI rat model, compared with the control group. Downregulation of miRNA145 increased cardiac cell apoptosis, suppressed phosphorylated (p)RACγ serine/threonineprotein kinase (Akt3) and pmechanistic target of rapamycin (mTOR) protein expression levels and suppressed autophagy in an in vitro model of AMI. However, overexpression of miRNA145 decreased cardiac cell apoptosis, induced pAkt3 and pmTOR protein expression and promoted autophagy in the in vitro model of AMI. The inhibition of Akt3 (GSK2110183, 1 nM) decreased the effect of the miRNA145 upregulation on cell apoptosis in the in vitro model of AMI. Chloroquine diphosphate (5 µM) inhibited the regulatory effect of miRNA145 upregulation on autophagy to adjust cell apoptosis, in the in vitro model of AMI. The results of the present study demonstrate that miRNA145 inhibits myocardial infarctioninduced apoptosis via autophagy associated with the Akt3/mTOR signaling pathway in vivo and in vitro.
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Apoptose/genética , Autofagia/genética , MicroRNAs/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Animais , Sequência de Bases , Modelos Animais de Doenças , Regulação para Baixo/genética , Lisossomos/metabolismo , Masculino , MicroRNAs/genética , Modelos Biológicos , Miocárdio/metabolismo , Miocárdio/patologia , Fosforilação , Ratos Sprague-Dawley , Regulação para Cima/genéticaRESUMO
Acute myocardial infarction induces ventricular remodeling, which is implicated in dilated heart and heart failure. The pathogenical mechanism of myocardium remodeling remains to be elucidated. The aim of the present study was to identify key genes and networks for myocardium remodeling following ischemiareperfusion (IR). First, the mRNA expression data from the National Center for Biotechnology Information database were downloaded to identify differences in mRNA expression of the IR heart at days 2 and 7. Then, weighted gene coexpression network analysis, hierarchical clustering, proteinprotein interaction (PPI) network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were used to identify key genes and networks for the heart remodeling process following IR. A total of 3,321 differentially expressed genes were identified during the heart remodeling process. A total of 6 modules were identified through gene coexpression network analysis. GO and KEGG analysis results suggested that each module represented a different biological function and was associated with different pathways. Finally, hub genes of each module were identified by PPI network construction. The present study revealed that heart remodeling following IR is a complicated process, involving extracellular matrix organization, neural development, apoptosis and energy metabolism. The dysregulated genes, including SRC protooncogene, nonreceptor tyrosine kinase, discs large MAGUK scaffold protein 1, ATP citrate lyase, RAN, member RAS oncogene family, tumor protein p53, and polo like kinase 2, may be essential for heart remodeling following IR and may be used as potential targets for the inhibition of heart remodeling following acute myocardial infarction.
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Regulação da Expressão Gênica , Redes Reguladoras de Genes , Traumatismo por Reperfusão Miocárdica , Miocárdio , Animais , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Miocárdio/patologia , RatosRESUMO
BACKGROUND: Mitogen-activated protein kinase-1 (MAPK1), as well as its downstream factors of hypoxia-inducible factor-1 (HIF-1) and heme oxygenase-1 (HO-1), have been documented to be involved in modulating development of coronary artery disease (CAD). HYPOTHESIS: Genetic mutations within the MAPK1/HIF-1/HO-1 signaling pathway could alter the risk of perimenopausal CAD in Chinese patients. METHODS: Peripheral blood samples were gathered from 589 CAD patients and 860 healthy controls, and 12 potential single-nucleotide polymorphisms (SNPs) were obtained from HapMap database and previously published studies. Genotyping of SNPs was implemented with the TaqMan SNP Genotyping Assays. Odds ratios (OR) and 95% confidence intervals (CI) were utilized to evaluate the correlations between SNPs and CAD risk. RESULTS: Regarding MAPK1 , rs6928 (OR: 1.71, 95% CI: 1.47-1.98, P < 0.05), rs9340 (OR: 0.85, 95% CI: 0.73-0.99, P < 0.05), and rs11913721 (OR: 0.70, 95% CI: 0.52-0.95, P < 0.05) were remarkably associated with susceptibility to perimenopausal CAD. Of these, rs9340 and rs11913721 were also regarded as protective factors for perimenopausal CAD patients. Moreover, results of HIF-1 indicated noticeable correlations between combined SNPs of rs1087314 and rs2057482 and risk of perimenopausal CAD (OR: 1.24, 95% CI: 1.01-1.53, P < 0.05; and OR: 0.71, 95% CI: 0.55-0.91, P < 0.05, respectively). Nonetheless, rs2071746 in HO-1 was found to be only associated with perimenopausal CAD risk (OR: 0.67, 95% CI: 0.58-0.78, P < 0.05). CONCLUSIONS: The genetic mutations within MAPK1 (rs6928, rs9340, rs11913721), HIF-1 (rs1087314, rs2057482), and HO-1 (rs2071746) could alter susceptibility to perimenopausal CAD in this Chinese population.
Assuntos
Doença da Artéria Coronariana/genética , Estenose Coronária/genética , Heme Oxigenase-1/genética , Fator 1 Induzível por Hipóxia/genética , Proteína Quinase 1 Ativada por Mitógeno/genética , Perimenopausa , Polimorfismo de Nucleotídeo Único , Transdução de Sinais/genética , Distribuição de Qui-Quadrado , China , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/enzimologia , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/enzimologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Razão de Chances , Fenótipo , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: The aim of this study was to validate the G.LAB MD2680 digital automatic blood pressure (BP) monitor according to major international protocols. PARTICIPANTS AND METHODS: The device was evaluated against auscultatory sphygmomanometry according to the European Society of Hypertension International Protocol (ESH-IP) revision 2010, the British Hypertension Society (BHS), and the International Organization for Standardization (ISO) 81060-2:2013 protocols. Bland-Altman plots were completed for systolic (SBP) and diastolic blood pressures (DBP), and the mean differences and SDs between the test device and the reference device were computed for all BP values. RESULTS: The G.LAB MD2680 passed the ESH-IP revision 2010 on 33 participants with a mean device-observer difference of 0.89±4.97 mmHg for SBP and 0.72±4.91 mmHg for DBP, respectively. The device achieved A/A grading for the BHS protocol among 85 participants with a device-observer difference of 0.70±6.35 mmHg for SBP and 0.62±6.41 mmHg for DBP, respectively. Furthermore, it also fulfilled the two criteria of the ISO 81060-2:2013 protocol. CONCLUSION: The G.LAB MD2680 digital automatic BP monitor fulfilled the accuracy requirements of the ESH-IP revision 2010 and the ISO 81060-2:2013 protocols, and achieved A/A grade of the BHS protocol, and it can be recommended for self-measurement in adults.
Assuntos
Determinação da Pressão Arterial/instrumentação , Monitores de Pressão Arterial , Idoso , Idoso de 80 Anos ou mais , Determinação da Pressão Arterial/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: The present study was intended to explore whether three proteins within MAPK signaling pathway (i.e. p38MAPK-1, HIF-1 and HO-1) were correlated with peri-menopausal women's coronary lesion features and prognosis. METHODS: Altogether 1449 peri-menopausal women were divided into non-coronary artery disease (CAD) group (n = 860) and CAD group (n = 589), including 167 pre-menopausal CAD populations and 422 post-menopausal CAD populations. General information about CAD risk parameters were gathered, including age, family history of CAD or hypertension or diabetes mellitus, bilirubin, cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) and so on. Coronary angiography results were judged, and CAD score was calculated with application of Genisin scoring method. Besides, detection of MAPK-1 levels was implemented with Strept Avidin-Biotin Complex (SABC) method, while HIF-1 and HO-1 expressions in the serum were determined utilizing ELISA detection kit. Correlations among protein expressions, characteristics of coronary lesions and prognosis of CAD populations were finally evaluated. RESULTS: Hypertension, hyperlipoidemia, diabetes and smoking history were more prevalent among postmenopausal CAD women than premenopausal CAD women (P < 0.05). Furthermore, postmenopausal women seemed to be significantly associated with multiple (i.e. double and triple) vessel lesions and severe lesion types (type B and C), when compared with premenopausal CAD group (P < 0.05). Similarly, remarkably elevated expressions of p38MAPK-1, HIF-1 and HO-1 were found within postmenopausal CAD populations in comparison to premenopausal ones (P < 0.05). The internal CysC, hs-CRP, TG and LDL-C concentrations all accorded with the following tendency: postmenopausal CAD women > premenopausal CAD women > non-CAD women. Moreover, p38MAPK-1, HIF-1 and HO-1 expressions were up-regulated with increasing number of vessel lesions and severity of coronary lesions among peri-menopausal women. Besides, among both pre-menopausal and post-menopausal CAD groups, positive correlations could be observed between MAPK-1 and TG (r s = 0.271; r s = 0.476), between HIF-1α and LDL-C (r s = 0.077; r s = 0.470), as well as between HO-1 and CysC (r s = 0.492; r s = 0.190) or hs-CRP (r s = 0.569; r s = 0.542) (all P < 0.05). MAPK-1, HIF-1α and HO-1 were also, respectively, positively correlated with CysC (r s = 0.415), hs-CRP (r s = 0.137), and TG (r s = 0.142), regarding post-menopausal CAD women (all P < 0.05). Finally, only SBP and TG were regarded as independent risk factors for CAD prognosis (i.e. high Genisin score) among premenopausal women (OR = 1.02, 95%CI: 1.01-1.18, P = 0.043; OR = 1.82, 95%CI: 1.01-3.33, P = 0.047). CONCLUSIONS: Expressions of p38MAPK-1, HIF-1 and HO-1 could serve as predictive roles for coronary lesions among peri-menopausal women.