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Background: The noninvasive computed tomography angiography-derived fractional flow reserve (CT-FFR) can be used to diagnose coronary ischemia. With advancements in associated software, the diagnostic capability of CT-FFR may have evolved. This study evaluates the effectiveness of a novel deep learning-based software in predicting coronary ischemia through CT-FFR. Methods: In this prospective study, 138 subjects with suspected or confirmed coronary artery disease were assessed. Following indication of 30%-90% stenosis on coronary computed tomography (CT) angiography, participants underwent invasive coronary angiography and fractional flow reserve (FFR) measurement. The diagnostic performance of the CT-FFR was determined using the FFR as the reference standard. Results: With a threshold of 0.80, the CT-FFR displayed an impressive diagnostic accuracy, sensitivity, specificity, area under the receiver operating characteristic curve (AUC), positive predictive value (PPV), and negative predictive value (NPV) of 97.1%, 96.2%, 97.7%, 0.98, 96.2%, and 97.7%, respectively. At a 0.75 threshold, the CT-FFR showed a diagnostic accuracy, sensitivity, specificity, AUC, PPV, and NPV of 84.1%, 78.8%, 85.7%, 0.95, 63.4%, and 92.8%, respectively. The Bland-Altman analysis revealed a direct correlation between the CT-FFR and FFR (p < 0.001), without systematic differences (p = 0.085). Conclusions: The CT-FFR, empowered by novel deep learning software, demonstrates a strong correlation with the FFR, offering high clinical diagnostic accuracy for coronary ischemia. The results underline the potential of modern computational approaches in enhancing noninvasive coronary assessment.
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Background: To determine the diagnostic performance of a novel computational fluid dynamics (CFD)-based algorithm for in situ CT-FFR in patients with ischemia-induced coronary artery stenosis. Additionally, we investigated whether the diagnostic accuracy of CT-FFR differs significantly across the spectrum of disease and analyzed the influencing factors that contribute to misdiagnosis. Methods: Coronary computed tomography angiography (CCTA), invasive coronary angiography (ICA), and FFR were performed on 324 vessels from 301 patients from six clinical medical centers. Local investigators used CCTA and ICA to conduct assessments of stenosis, and CT-FFR calculations were performed in the core laboratory. For CCTA and ICA, CT-FFR ≤ 0.8 and a stenosis diameter ≥ 50% were identified as lesion-specific ischemia. Univariate logistic regression models were used to assess the effect of features on discordant lesions (false negative and false positive) in different CT-FFR categories. The diagnostic performance of CT-FFR was analyzed using an invasive FFR ≤ 0.8 as the gold standard. Results: The Youden index indicated an optimal threshold of 0.80 for CT-FFR to identify functionally ischemic lesions. On a per-patient basis, the diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for CT-FFR were 96% (91%-98%), 92% (87%-96%), 94% (90%-96%), 91% (85%-95%), and 96% (92%-99%), respectively. The diagnostic efficacy of CT-FFR was higher than that of CCTA without the influence of calcification. Closer to the cut point, there was less certainty, with the agreement between the invasive FFR and the CT-FFR being at its lowest in the CT-FFR range of 0.7-0.8. In all lesions, luminal stenosis ≥ 50% significantly affected the risk of reduced false negatives (FN) and false positives (FP) results by CT-FFR, irrespective of the association with calcified plaque. Conclusions: In summary, CT-FFR based on the new parameter-optimized CFD model has a better diagnostic performance than CTA for lesion-specific ischemia. The presence of calcified plaque has no significant effect on the diagnostic performance of CT-FFR and is independent of the degree of calcification. Given the range of applicability of our software, its use at a CT-FFR of 0.7-0.8 requires caution and must be considered in the context of multiple factors.
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BACKGROUND AND AIMS: Computed tomography-derived fractional flow reserve (CT-derived FFR) algorithms have emerged as promising noninvasive methods for identifying hemodynamically significant coronary artery disease (CAD). However, its broad adaption is limited by the complex workflow, slow processing, and supercomputer requirement. Therefore, CT-derived FFR solutions capable of producing fast and accurate results could help deliver time-sensitive results rapidly and potentially alter patient management. The current study aimed to determine the diagnostic performance of a novel CT-derived FFR algorithm, esFFR, on patients with CAD was evaluated. METHODS: 329 patients from 6 medical centers in China were included in this prospective study. CT-derived FFR calculations were performed on 350 vessels using the esFFR algorithm using patients' presenting coronary computed tomography angiography (CCTA) images, and results and processing speed were recorded. Using invasive FFR measurements from direct coronary angiography as the reference standard, the diagnostic performance of esFFR and CCTA in detecting hemodynamically significant lesions were compared. Post-hoc analyses were performed for patients with calcified lesions or stenoses within the CT-derived FFR diagnostic "gray zone." RESULTS: The esFFR values correlated well with invasive FFR. The sensitivity, specificity, accuracy, positive and negative predictive value for esFFR were all above 90%. The overall performance of esFFR was superior to CCTA. Coronary calcification had minimal effects on esFFR's diagnostic performance. It also maintained 85% of diagnostic accuracy for "gray zone" lesions, which historically was <50%. The average esFFR processing speed was 4.6 ± 1.3 minutes. CONCLUSIONS: The current study demonstrated esFFR had high diagnostic efficacy and fast processing speed in identifying hemodynamically significant CAD.
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BACKGROUND: Non-ST-segment elevation myocardial infarction (NSTEMI) is a common form of acute myocardial infarction and rapid and accurate diagnosis is crucial for timely treatment. Current guidelines recommend using high-sensitivity cardiac troponin (hs-cTn) assays to determine circulating cTnI or cTnT levels. While the accuracy of the 0 h/1 h algorithm for diagnosing NSTEMI in different regions and patient populations remains controversial. Additionally, point-of-care testing (POCT) cTn assays have the potential to provide troponin readings to physicians within 15 min, but their accuracy in diagnosing NSTEMI in the emergency department (ED) requires further investigation. METHODS: A single-center prospective observational cohort study was conducted at Shaanxi Provincial People's Hospital to assess the analytical and diagnostic performance of the laboratory-based Roche Modular E170 hs-cTnT using the 0 h/1 h algorithm with Radiometer AQT90-flex POCT cTnT assay in undifferentiated chest pain patients presenting to the ED. Whole-blood samples were collected and hs-cTnT and POCT cTnI were measured simultaneously at baseline and after 1 h. RESULTS: The study results showed that the POCT cTnT assay using the 0 h/1 h algorithm had comparable diagnostic accuracy to the laboratory-based Roche Modular E170 hs-cTnT assay in diagnosing NSTEMI in patients with chest pain. CONCLUSION: The laboratory-based Roche Modular E170 hs-cTnT using the 0 h/1 h algorithm is reliable and accurate method for diagnosing NSTEMI in undifferentiated chest pain patients presenting to the ED. POCT cTnT assay has comparable diagnostic accuracy to the hs-cTnT assay and its rapid turnaround time makes it a valuable tool in expediting the diagnostic workup of chest pain patients.
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Infarto do Miocárdio sem Supradesnível do Segmento ST , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico , Estudos Prospectivos , Dor no Peito/diagnóstico , Dor no Peito/etiologia , Troponina T , Troponina I , Algoritmos , Serviço Hospitalar de Emergência , BiomarcadoresRESUMO
Recently, the application of lignin activation by demethylation to improve reactivity and enrich multiple functions has intensively attracted attention. However, it is still challenge up to now due to the low reactivity and complexity of lignin structure. Here, an effective demethylation way was explored by microwave-assisted method for substantially enhancing the hydroxyl (-OH) content and retaining the structure of lignin. Then, the optimum demethylated lignin was used to removal heavy metal ions and promote wound healing, respectively. In detail, for microwave-assisted demethylated poplar lignin (M-DPOL), the contents of phenolic (Ar-OH) and total hydroxyl (Tot-OH) groups reached the maximum for 60 min at 90 °C in DMF with 7.38 and 9.13 mmol/g, respectively. After demethylation, with this M-DPOL as lignin-based adsorbent, the maximum adsorption capacity (Qmax) for Pb2+ ions reached 104.16 mg/g. Based on the isotherm, kinetic and thermodynamic models analyses, the chemisorption occurred in monolayer on the surface of M-DPOL, and all adsorption processes were endothermic and spontaneous. Meanwhile, M-DPOL as a wound dressing had excellent antioxidant property, outstanding bactericidal activity and remarkable biocompatibility, suggesting that it did not interfere with cell proliferation. Besides, the wounded rats treated with M-DPOL significantly promoted its formation of re-epithelialization and wound healing of full-thickness skin defects. Overall, microwave-assisted method of demethylated lignin can offer great advantages for heavy metal ions removal and wound care dressing, which facilitates high value application of lignin.
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Metais Pesados , Poluentes Químicos da Água , Ratos , Animais , Lignina/química , Adsorção , Metais Pesados/química , Íons , Bandagens , Poluentes Químicos da Água/química , CinéticaRESUMO
Introduction: Red cell distribution width (RDW) reflects the heterogeneity of red blood cell size. However, few studies examined whether RDW is related to glucose metabolism indices, such as fasting blood glucose (FBG) and hemoglobin A1c (HbA1c), diabetic mellitus (DM) state or long-term outcomes of acute coronary syndrome (ACS) patients. Methods and Results: A total of 448 consecutive patients with ACS were enrolled in this study. All patients were followed up for major cardiovascular adverse events (MACEs), and the mean follow-up was 952 days. Linear regression analysis showed that RDW inversely correlated with FBG but not HbA1c or DM. Kaplan-Meier survival curve analysis demonstrated that higher RDW levels were significantly positively associated with MACEs in the whole study population and the ACS patients with high FBG but not the low FBG group. Cox multivariate regression analysis revealed the independent function of RDW on MACEs in all ACS patients and ACS patients with high FBG. The receiver operating characteristic (ROC) curve demonstrated the optimal cutoff value of RDW for MACEs. Conclusion: We first reported that higher RDW was associated with decreased FBG but not HbA1c or DM and an increased risk of MACEs in patients with ACS. This relationship was also found in ACS patients with higher FBG levels but not in ACS patients with lower FBG.
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Background: Coronary bifurcation lesions are common of percutaneous coronary intervention (PCI), and the optimal interventional therapy strategy is still a matter of debate and remains a challenge for interventional cardiologists. The provisional stenting technique is still a preferred method for most bifurcation lesions, but restenosis of the side branch (SB) occurs in approximately 17-19% of cases. Therefore, the dilemma of reducing SB restenosis still exists, and further research on strategies to reduce restenosis for SB is necessary. Drug-coated balloon (DCB) can reduce clinical events in small vessel disease and in-stent restenosis. The efficacy and safety of DCB for SB of true coronary bifurcation lesions have not been fully investigated. A randomized comparison of DCB combined with cutting balloon angioplasty vs. cutting balloon angioplasty for SB has never been published. Methods and design: The purpose of this study is to explore the superiority of DCB combined with cutting balloon vs. cutting balloon angioplasty for SB after main vessel (MV) drug-eluting stent implantation of true coronary bifurcation lesions. This study is a multicenter, prospective, randomized controlled trial including 140 patients with true coronary bifurcation lesions. Patients will be randomized in a 1:1 manner to receive either DCB combined with cutting balloon or cutting balloon angioplasty for SB after MV drug-eluting stent implantation. The primary endpoint is the evaluation of late lumen loss (LLL) of SB at the 9-month follow-up. The secondary endpoints include procedural success during initial hospitalization, LLL of MV at the 9-month follow-up, binary angiographic restenosis in MV and SB at the 9-month follow-up, the proportion of patients with a final post-PCI quantitative flow ratio result ≤ 0.80 for SB at the 9-month follow-up, and major adverse cardiac events during the 24-month follow-up. Conclusions: This clinical trial will provide evidence as to whether DCB combined with cutting balloon for SB of true coronary bifurcation lesions is a superior treatment approach. Trial Registration Number: ChiCTR2000040475. Dissemination: The results of this clinical trial will be published in a peer-reviewed journal.
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Apêndice Atrial , Doença da Artéria Coronariana , Traumatismos Cardíacos , Eletrodos , HumanosRESUMO
Background: Coronary pressure-derived fractional flow reverse (FFR) is the standard of the functional assessment of lesion severity. In spite of its strengths in determining ischemia-related coronary stenosis, the invasive operation involved still limits its clinical application. Coronary computed tomography angiography-derived FFR (CCTA-FFR) or computed tomography-derived FFR (CT-FFR) has been indicated as an effective and non-invasive index to evaluate lesion-specific ischemia. However, its diagnostic performance, especially in patients with different severity of coronary stenosis, remains unknown. The current research attempted to demonstrate this problem and provided the foundation for extensive clinical application of CCTA-FFR. Methods: The design of this study was a diagnostic test. A total of 97 vessels from 91 patients who performed CCTA and coronary angiography (CAG) during a hospitalization collected from two research centers were included in this study. CCTA-FFR and FFR were obtained by CCTA and CAG separately. The Gensini score was calculated according to the CAG in each patient. FFR was indicated as the golden diagnosis of lesion-specific ischemia with a cut-off value of 0.80, which was consistent with most contemporary studies. A receiver-operating characteristic (ROC) curve, simple linear analysis, and Bland-Altman plot were performed to determine the diagnostic performance of CCTA-FFR. Results: CCTA-FFR was well correlated with invasive FFR (R2=0.745, P<0.001) and the area under the curve (AUC) was 0.976. The sensitivity was 94.6% and the specificity was 95.1%. The mean difference between FFR and CT-FFR was 0.011, and the 95% confidence interval was -0.173 to 0.196. The AUCs were 0.989 and 0.928 in the low and high Gensini groups, respectively, and there was no significant difference in the diagnostic accuracies between these two groups (Z=0.003, P>0.500). CT-FFR still exhibited a good correlation with FFR (R2=0.713, P<0.001 in the low Gensini group and R2=0.743, P<0.001 in the high Gensini group). The systematic differences were calculated, and the mean difference between FFR and CT-FFR was -0.005 and 0.025, respectively, in these two groups. Conclusions: CCTA-FFR exhibited good diagnostic performance in patients with different Gensini score levels. Our results indicate that CCTA-FFR could be an effective tool to screen lesion-specific ischemia in patients with coronary artery disease.
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AIMS: Although accumulating evidence demonstrated that virtual fractional flow reserve (FFR) based on coronary computed tomography angiography (CCTA) (CT-FFR) or invasive coronary angiogram (ICA) (CA-FFR) are promising alternatives to wire based FFR, which method has better diagnostic accuracy was still unclear. In our study, we aim to directly compare the diagnostic performance of CT-FFR and CA-FFR. METHODS: During the period of September 2019 to December 2020, patients with at least one 30%-90% coronary artery stenosis were enrolled and received invasive FFR. Then, virtual FFR values were calculated based on both CCTA and ICA, and then compared with the invasive FFR value. RESULTS: Invasive FFR measurements were successfully performed in 114 vessels of 96 patients. Both CT-FFR and CA-FFR showed good correlation with wire-based FFR, with r values of 0.84 and 0.71 respectively. In paired t-test, the deviation of CT-FFR and CA-FFR was not significantly different (tâ¯=â¯-1.9083, pâ¯=â¯0.05889). In Bland-Altman analysis, the coefficients of variation were 8.4% and 13.2% for CT-FFR and CA-FFR respectively. In ROC curve analysis, the per-vessel diagnostic accuracy of CT-FFR and CA-FFR was 94.7% and 92.1% respectively. The area under the curve of CT-FFR was slightly higher than that of CA-FFR (0.986 and 0.916 respectively, the difference between areasâ¯=â¯0.070, 95% CI 0.003-0.137, pâ¯=â¯0.0227). CONCLUSION: Both CT-FFR and CA-FFR had good diagnostic concordance with wire-based FFR. In ROC Curve analysis, CT-FFR demonstrated slightly higher diagnostic accuracy than CA-FFR. CLINICAL TRIAL REGISTRATION: URL: https://www.chictr.org.cn/showproj.aspx?proj=44719. Unique Identifier: ChiCTR1900026971.
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Background: The classic electrocardiogram (ECG) criteria have been applied to left ventricular hypertrophy (LVH) screening but have low sensitivity. Recently, the newly proposed Peguero-Lo Presti criterion has been proven to be more sensitive in detecting LVH in patients with hypertension than several current ECG criteria. The diagnostic value of the Peguero-Lo Presti criterion in hypertrophic cardiomyopathy (HCM) patients has not been fully evaluated. This study aims to test whether the new Peguero-Lo Presti criterion can improve the diagnostic performance in patients with HCM. Methods: This study included HCM patients and sex-and age-matched healthy control subjects. The diagnostic performance of the Peguero-Lo Presti criterion was evaluated along with the Sokolow-Lyon criterion, Cornell criterion, and total 12-lead voltage criterion. Results: Overall, 63 HCM patients and 63 controls were enrolled. The diagnostic accuracy, sensitivity and specificity of Peguero-Lo Presti criterion were 74.6%, 73.0% and 76.2%, respectively. The Peguero-Lo Presti criterion had the highest sensitivity, while the Cornell criterion and Sokolow-Lyon criterion had the highest specificity (96.8%). The area under the curve (AUC) showed that the Peguero-Lo Presti criterion was 0.809 (95% CI, 0.730-0.874; p < 0.0001), Sokolow-Lyon criterion was 0.841 (95% CI, 0.766-0.900) and total 12-lead voltage criterion was 0.814 (95% CI, 0.735-0.878). There was no significant difference in AUC between Peguero-Lo Presti criterion and Sokolow-Lyon criterion (p = 0.533), or Peguero-Lo Presti criterion and total 12-lead voltage criterion (p = 0.908). Receiver operator characteristic curve analysis of the Peguero-Lo Presti criterion showed an optimal cutoff of > 3.15 mV for men (sensitivity: 63.9%; specificity: 80.0%) and > 2.29 mV for women (sensitivity: 78.6%; specificity: 85.7%). Conclusions: The Peguero-Lo Presti criterion provides high sensitivity for ECG diagnosis of HCM patients and can be considered when applicable but this needs to be verified in a larger population.
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Bloqueio Atrioventricular/etiologia , Procedimentos Cirúrgicos Cardíacos/métodos , Ecocardiografia/métodos , Eletrocardiografia , Neoplasias Cardíacas/complicações , Mixoma/complicações , Bloqueio Atrioventricular/diagnóstico , Diagnóstico Diferencial , Átrios do Coração , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Mixoma/diagnóstico , Mixoma/cirurgiaRESUMO
Mitochondrial injury plays an essential role in the pathogenesis of diabetic cardiomyopathy (DCM). Previous studies demonstrated that rosmarinic acid (RA) treatment prevented high glucose-induced mitochondrial injury in vitro. However, whether RA can ameliorate cardiac function by preventing mitochondrial injury in DCM is unknown. The SIRT1/PGC-1α pathway has emerged as an important regulator of metabolic control and other mitochondrial functions. The present study was undertaken to determine the effects of RA on mitochondrial and cardiac function in DCM as well as the involvement of the SIRT1/PGC-1α pathway. Our results revealed that RA improved cardiac systolic and diastolic function and prevented mitochondrial injury in DCM, as shown by the reduced blood glucose and lipid levels, increased mitochondrial membrane potential levels, improved adenosine triphosphate synthesis, and inhibited apoptosis (P < 0.05). Moreover, RA upregulated the expression of SIRT1 and PGC-1α in DCM mice and high glucose-treated H9c2 cardiomyocytes (P < 0.05). Further mechanistic studies in H9c2 cardiomyocytes revealed that suppression of SIRT1 by Sh-SIRT1 counteracted the effects of RA on high glucose-induced abnormal metabolism of glucose and lipids, oxidative stress and apoptosis (P < 0.05). Taken together, these data indicate that RA prevented mitochondrial injury and cardiac dysfunction in DCM mice, and the SIRT1/PGC-1α pathway mediated the protective effects of RA.
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Cinamatos/uso terapêutico , Depsídeos/uso terapêutico , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/fisiopatologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Sirtuína 1/metabolismo , Animais , Apoptose/efeitos dos fármacos , Cinamatos/antagonistas & inibidores , Cinamatos/farmacologia , Depsídeos/antagonistas & inibidores , Depsídeos/farmacologia , Glucose/farmacologia , Masculino , Camundongos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/antagonistas & inibidores , Ácido RosmarínicoRESUMO
OBJECTIVE: To evaluate the effect of rosmarinic acid (RA) on mitophagy and hypertrophy of cardiomyocytes exposed to high glucose (HG). METHODS: Rat cardiomyocytes (H9c2) exposed to HG (25 mmol/L) were treated with 50 µmol/L RA or with both RA treatment and Parkin siRNA transfection, with the cells cultured in normal glucose (5.5 mmol/L) and HG as the controls. The expressions of PINK1, Parkin and LC3II/LC3I in the cells were detected by Western blotting. The formation of mitochondrial autophagosomes was observed by transmission electron microscope. Flow cytometry was employed to detect the level of reactive oxygen species (ROS) and apoptotic rate of the cells. The activities of respiratory chain complex enzymes were measured by spectrophotometry. Fluorescence enzyme labeling and 3H-leucine labeling were used for determining the level of membrane potential and protein synthesis rate, respectively. The cell surface area was observed by light microscopy. RESULTS: RA treatment significantly increased the expression levels of PINK1, Parkin and LC3-II/I (P < 0.05), promoted the formation of mitochondrail autophagosome, inhibited the production of reactive oxygen species (P < 0.05), restored the activities of mitochondrial respiratory chain complex enzymes and mitochondrial membrane potential (P < 0.05), inhibited apoptosis (P < 0.05), and reduced the cell surface area and protein synthesis rate of H9c2 cells induced by HG exposure (P < 0.05). The protective effects of RA against HG-induced oxidative stress and cardiomyocyte hypertrophy was obviously blocked by inhibition of mitophagy mediated by transfection with Parkin siRNA (P < 0.05). CONCLUSIONS: RA can protect rat cardiomyocytes against oxidative stress injury and cardiomyocyte hypertrophy induced by HG by activating Parkin-mediated mitophagy.
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Mitofagia , Miócitos Cardíacos , Animais , Cinamatos , Depsídeos , Glucose , Hipertrofia , Proteínas Quinases , Ratos , Espécies Reativas de Oxigênio , Ubiquitina-Proteína Ligases/genética , Ácido RosmarínicoRESUMO
Oxidative stress and inflammation are involved in the pathogenesis of atherosclerosis. Calcium channel blockers (CCBs) inhibit the development of atherosclerosis, although the underlying molecular basis has not been completely elucidated. The present study was designed to investigate the effects of felodipine, a CCB, on inflammation and oxidative stress in human umbilical vein endothelial cells (HUVECs) and to examine the underlying mechanisms of action. Oxidized lowdensity lipoprotein (oxLDL) was used to induce an inflammatory response in HUVECs. The effects of felodipine were investigated by measuring the content of nitric oxide (NO) and reactive oxygen species (ROS), the mRNA and protein levels of intercellular adhesion molecule 1 (ICAM1) and vascular cell adhesion protein 1 (VCAM1), and the mRNA levels of endothelial NO synthase (eNOS) and inducible NO synthase (iNOS), in addition to the adhesion ability of U937 cells to HUVECs. ROS and NO levels were significantly increased in HUVECs following 24h treatment with 25 mg/l oxLDL (P<0.01). The increase in ROS was reversed by treatment with felodipine. In addition, NO levels were increased following treatment with 1 µmol/l felodipine (P<0.05). The mRNA expression of ICAM1, VCAM1, eNOS and iNOS was increased (P<0.05). Administration of 0.1 µM felodipine significantly decreased the expression of ICAM1, VCAM1, and iNOS (P<0.05). The number of U937 cells adhered to oxLDLtreated HUVECs was significantly increased compared with control, which was reversed by felodipine (0.1 µM). In conclusion, felodipine was demonstrated to inhibit oxidative stress and inflammatory responses, suggesting that it may be used to treat atherosclerosis.
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Felodipino/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Inflamação/metabolismo , Lipoproteínas LDL/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/tratamento farmacológico , Inflamação/genética , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
A great number of basic and clinical studies have demonstrated that inflammatory cytokines play an important role in the development and progression of chronic heart failure (CHF). However, there is limited information about the role of novel cytokine interleukin-37 (IL-37) in heart failure. We measured plasma IL-37 levels by enzyme-linked immunosorbent assay (ELISA) in 158 patients with chronic heart failure and 30 control subjects. Our results showed that plasma IL-37 levels were significantly elevated in patients with CHF compared with healthy controls (143.73 ± 26.83 pg/ml versus 45.2 ± 11.56 pg/ml, P < 0.001). Furthermore, plasma IL-37 levels were positively correlated with hs-CRP, hs-TnT, and NT-proBNP and negatively correlated with left ventricular ejection function (LVEF). 11 patients died of cardiovascular cause, and 27 HF patients were rehospitalized for worsening HF within 12 months. Multivariate Cox regression analysis showed that plasma IL-37 is an independent predictor of major adverse cardiac events (MACE). Furthermore, CHF patients with >99 pg/ml plasma IL-37 had significantly higher incidences of MACE within 12 months. Our data suggest that plasma IL-37 may play a role in the pathogenesis of CHF and may be a novel predictor of poor prognosis in HF patients.
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Insuficiência Cardíaca/sangue , Interleucina-1/sangue , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Função Ventricular EsquerdaRESUMO
INTRODUCTION: Angiopoietin-2 (Ang-2) plays a critical role in inducing tumor cell infiltration, and this invasive phenotype is caused by up-regulation of matrix metalloproteinase (MMP)-2. The relationship between Ang-2 and MMP-2 in atherosclerosis has not been reported yet. The aim is to measure the plasma concentrations of Ang-1, Ang-2 and MMP-2 and assess the correlation between the concentrations of these factors in coronary heart disease (CHD) patients. MATERIAL AND METHODS: The testing was done in a cross-sectional study. We prospectively enrolled 42 individuals with acute myocardial infarction, 42 individuals with unstable angina pectoris, 42 individuals with stable angina pectoris and 45 healthy control subjects. Concentrations of Ang-1, Ang-2 and MMP-2 were measured using the enzyme-linked immunosorbent assay (ELISA) method. Spearman's rank correlation was calculated to evaluate the relationships between MMP-2 and Ang-1, and MMP-2 and Ang-2 in patients with CHD. RESULTS: Patients with acute myocardial infarction and unstable angina pectoris had higher Ang-2 and MMP-2 levels compared with stable angina patients and healthy control subjects (p < 0.05), while concentrations of Ang-1 were not statistically different between the groups. Spearman's rank correlation showed that Ang-2 levels positively correlated with MMP-2 in patients with CHD (r = 0.679, p < 0.001). CONCLUSIONS: Plasma Ang-2 and MMP-2 levels but not Ang-1 levels were increased in patients with CHD. Ang-1 correlated weakly with MMP-2, whereas the Ang-2 and MMP-2 correlation was strong in patients with CHD. Ang-2 may play a role in atherosclerosis, and have an interaction with MMP-2.
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Serotonin (5-HT) has been shown to be involved in pulmonary vascular remodeling in pulmonary arterial hypertension (PAH) by inducing pulmonary artery smooth muscle cells (PASMCs) proliferation and inhibiting PASMC apoptosis. Peroxisome proliferator-activated receptor γ (PPARγ) plays a crucial role in regulating proliferation and apoptosis of many cell types. Moreover, recently, loss of PPARγ has also been reported to be associated with the development of PAH. The present study is aimed to assess whether PPARγ is involved in 5-HT induced PASMC proliferation and apoptosis inhibition and the possible mechanism. We found that 5-HT could induce PASMC proliferation and inhibit PASMC apoptosis in a dose-dependent manner. Furthermore, we found that 5-HT negatively regulated PPARγ expression and gene promoter activity in PASMCs and 5-HT induced PASMC proliferation and apoptosis resistance could be abolished by PPARγ agonists and enhanced by PPARγ inhibitor. In addition, we found that extracellular signal-regulated kinase (ERK) signaling pathway mediated the 5-HT-induced inhibition of PPARγ expression. Our results might provide novel insights into the mechanisms for the pro-remodeling action of 5-HT in pulmonary vasculature.
Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , PPAR gama/metabolismo , Serotonina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Músculo Liso Vascular/enzimologia , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/enzimologia , Miócitos de Músculo Liso/patologia , PPAR gama/efeitos dos fármacos , PPAR gama/genética , Regiões Promotoras Genéticas , Inibidores de Proteínas Quinases/farmacologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/enzimologia , Artéria Pulmonar/patologia , RNA Mensageiro/metabolismoRESUMO
BACKGROUND: Fibroblast growth factor 21 (FGF-21), a newly discovered adipokine, plays an important role in glucose and lipid metabolism and is associated with the development of metabolic disorders, such as obesity, and cardiovascular diseases. This study aimed to investigate the association of serum FGF-21 levels with the presence of atrial fibrillation (AF). METHODS: Total 113 patients with AF and 60 healthy control subjects were enrolled. All AF cases were categorized into paroxysmal, persistent and permanent AF. Serum levels of FGF-21, high-sensitivity C-reactive protein (hs-CRP) and other routine biochemical parameters were measured. RESULTS: Serum FGF-21 levels were significantly higher in AF patients than in controls (250.12±78.48 vs. 144.15±56.31pg/mL, P<0.001), and hs-CRP levels were significantly higher in AF patients than in controls (2.36±1.10 vs. 1.24±0.82, P<0.05). In subgroup studies, patients with permanent AF had higher serum FGF-21 levels than those with persistent and paroxysmal AF. After the adjustment of the age, gender and body mass index, serum FGF-21 levels were positively correlated with left atrial diameter (LAD) (P<0.01). A multivariate logistic regression analysis showed that FGF-21, LAD and hs-CRP were correlated with AF (P<0.05). CONCLUSIONS: Our data demonstrate that serum FGF-21 levels are elevated in AF patients and associated with atrial remolding, independent of established risk factors such as C-reactive protein.
Assuntos
Fibrilação Atrial/sangue , Fatores de Crescimento de Fibroblastos/sangue , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Autophagy, a conservative degradation process for long-lived and damaged proteins, participates in a variety of biological processes including obesity. However, the precise mechanism of action behind obesity-induced changes in autophagy still remains elusive. This study was designed to examine the role of the antioxidant catalase in high fat diet-induced changes in cardiac geometry and function as well as the underlying mechanism of action involved with a focus on autophagy. Wild-type (WT) and transgenic mice with cardiac overexpression of catalase were fed low or high fat diet for 20 weeks prior to assessment of myocardial geometry and function. High fat diet intake triggered obesity, hyperinsulinemia, and hypertriglyceridemia, the effects of which were unaffected by catalase transgene. Myocardial geometry and function were compromised with fat diet intake as manifested by cardiac hypertrophy, enlarged left ventricular end systolic and diastolic diameters, fractional shortening, cardiomyocyte contractile capacity and intracellular Ca²âº mishandling, the effects of which were ameliorated by catalase. High fat diet intake promoted reactive oxygen species production and suppressed autophagy in the heart, the effects of which were attenuated by catalase. High fat diet intake dampened phosphorylation of inhibitor kappa B kinase ß(IKKß), AMP-activated protein kinase (AMPK) and tuberous sclerosis 2 (TSC2) while promoting phosphorylation of mTOR, the effects of which were ablated by catalase. In vitro study revealed that palmitic acid compromised cardiomyocyte autophagy and contractile function in a manner reminiscent of fat diet intake, the effect of which was significantly alleviated by inhibition of IKKß, activation of AMPK and induction of autophagy. Taken together, our data revealed that the antioxidant catalase counteracts against high fat diet-induced cardiac geometric and functional anomalies possibly via an IKKß-AMPK-dependent restoration of myocardial autophagy. This article is part of a Special Issue entitled: Autophagy and protein quality control in cardiometabolic diseases.