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1.
BMC Cardiovasc Disord ; 24(1): 261, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769478

RESUMO

BACKGROUND: Pheochromocytoma is rare in pregnant women. It presents as diverse symptoms, including hypertension and sweating. The symptoms of pregnant women with pheochromocytoma and comorbid hypertension often mimic the clinical manifestations of preeclampsia, and these women are often misdiagnosed with preeclampsia. CASE PRESENTATION: In this case, a pregnant woman presented with chest pain as the primary symptom, and a diagnosis of pheochromocytoma was considered after ruling out myocardial ischemia and aortic dissection with the relevant diagnostic tools. This patient then underwent successful surgical resection using a nontraditional management approach, which resulted in a positive clinical outcome. CONCLUSIONS: It is essential to consider pheochromocytoma as a potential cause of chest pain and myocardial infarction-like electrocardiographic changes in pregnant women, even if they do not have a history of hypertension.


Assuntos
Neoplasias das Glândulas Suprarrenais , Feocromocitoma , Complicações Neoplásicas na Gravidez , Humanos , Feocromocitoma/complicações , Feocromocitoma/diagnóstico , Feocromocitoma/cirurgia , Feminino , Gravidez , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/cirurgia , Neoplasias das Glândulas Suprarrenais/diagnóstico , Complicações Neoplásicas na Gravidez/diagnóstico , Complicações Neoplásicas na Gravidez/cirurgia , Adulto , Resultado do Tratamento , Dor no Peito/etiologia , Dor no Peito/diagnóstico , Valor Preditivo dos Testes , Adrenalectomia , Eletrocardiografia
2.
BMC Cardiovasc Disord ; 23(1): 92, 2023 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-36803298

RESUMO

BACKGROUND: A sudden increase in heart rate (HR) during ablation of the right superior pulmonary venous vestibule (RSPVV) is often detected in patients undergoing circumferential pulmonary vein isolation (CPVI). In our clinical practices, we observed that some patients had few complaints of pain during the procedures under conscious sedation. AIM: We aimed to investigate whether there is a correlation between a sudden increase in HR during AF ablation of the RSPVV and pain relief under conscious sedation. METHODS: We prospectively enrolled 161 consecutive paroxysmal AF patients who underwent the first ablation from July 1, 2018, to November 30, 2021. Patients were assigned to the R group when they had a sudden increase in HR during the ablation of the RSPVV, and the others were assigned to the NR group. Atrial effective refractory period and HR were measured before and after the procedure. Visual Analogue Scale (VAS) scores, vagal response (VR) during ablation, and the amount of fentanyl used were also documented. RESULTS: Eighty-one patients were assigned to the R group, and the remaining 80 were assigned to the NR group. The post-ablation HR (86.3 ± 8.8 vs. 70.0 ± 9.4 b/min; p ≤ 0.001) was higher in the R group than in pre-ablation. Ten patients in the R group had VRs during CPVI, as well as 52 patients in the NR group. The VAS score [2.3 (1.3-3.4) vs. 6.0 (4.4-6.9); p ≤ 0.001)] and the amount of fentanyl used (107 ± 12 vs. 172 ± 26 ug; p ≤ 0.001) were significantly lower in the R group. CONCLUSION: A sudden increase in HR during the ablation of the RSPVV was correlated with pain relief in patients undergoing AF ablation under conscious sedation.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Frequência Cardíaca , Veias Pulmonares/cirurgia , Resultado do Tratamento , Dor , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos
3.
Int Heart J ; 64(4): 543-550, 2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37460321

RESUMO

Multiple reports relate new-onset atrial fibrillation (NOAF) to poor clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) who received percutaneous coronary intervention (PCI). The prognostic nutritional index (PNI) is a reliable indicator of immunonutritional-inflammatory status, and it is linked to clinical outcomes in cardiovascular disease patients. This research aims to explore the relationship between NOAF and PNI.Overall, 600 STEMI patients treated with PCI were recruited for this retrospective analysis. The patients were categorized into the NOAF group or sinus rhythm (SR) group. Logistic regression and receiver operating characteristic (ROC) curve analyses were conducted to assess PNI estimation. Lastly, the Kaplan-Meier curve was used to compare all-cause mortality between both groups.The combined NOAF incidence in PCI-treated STEMI patients was 7.7%. PNI was independently correlated with NOAF using multivariate regression analyses (odds ratio [OR], 0.824; 95% confidence interval [CI], 0.750-0.906; P < 0.001). In ROC curve analyses, the best PNI threshold value for predicting NOAF was 40.1, with sensitivity, and specificity of 76.09% and 71.30%, respectively area under the curve, 0.787; 95% CI, 0.752-0.819; P < 0.001). After a median of 41-month follow-up, the Kaplan-Meier curve revealed that the NOAF patients displayed an elevated all-cause death incidence compared with SR patients, with a log-rank of P = 0.005.This study demonstrated that PNI is an independent predictor of NOAF in STEMI patients during hospitalization after PCI, which is strongly correlated with a poor outcome upon discharge.

4.
BMC Cardiovasc Disord ; 22(1): 335, 2022 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-35902799

RESUMO

BACKGROUND: Intermediate-risk acute pulmonary embolism (APE) patients are usually defined as hemodynamically stable, comprehending a great therapeutic dilemma. Although anticoagulation therapy is sufficient for most intermediate-risk APE patients, some patients can deteriorate and eventually require a systemic fibrinolytic agent or thrombectomy. Hence, this study aimed to evaluate the predictive value of differences in clinical data for the short-term prognosis of intermediate-risk APE patients. METHODS: A retrospective cohort of 74 intermediate-risk APE patients confirmed by computed tomography pulmonary angiography was analyzed in the present study. Adverse clinical event outcomes included PE-related in-hospital deaths, critical systolic blood pressure consistently under 90 mmHg, refractory to volume loading and vasopressor infusion requirements, mechanical ventilation, and cardiopulmonary resuscitation. The APE patients were stratified into two groups: adverse outcome (n = 25) and control (n = 49) groups. Then, the clinical data of the two groups were compared. Receiver operating characteristic (ROC) curves were used to explore the predictive value of white blood cell (WBC) counts and the right to left ventricular short-axis (RV/LV) ratio. Model calibration was assessed using the Hosmer-Lemeshow goodness-of-fit statistic. RESULTS: The brain natriuretic peptide, WBC count, and the RV/LV ratio were higher in patients with adverse outcomes compared to controls. The APE patients with adverse outcomes presented significantly higher rates of syncope, Negative T waves (NTW) in V1-V3, intermediate-high risk, thrombolytic therapy, and low arterial oxygen saturation (SaO2) compared to controls. In the multivariate logistic regression analysis, the SaO2 < 90%, [odds ratio (OR) 5.343, 95% confidence interval (CI) 1.241-23.008; p = 0.024], RV/LV ratio (OR 7.429, 95% CI 1.145-48.209; p = 0.036), Syncope (OR 12.309, 95% CI 1.702-89.032; p = 0.013), NTW in V1-V3 (OR 5.617, 95% CI 1.228-25.683; p = 0.026), and WBC count (OR 1.212, 95% CI 1.035-1.419; p = 0.017) were independent predictors of in-hospital adverse outcomes among APE patients. The ROC curve analysis indicated that the RV/LV ratio can be used to predict adverse outcomes (AUC = 0.748, p < 0.01) and calibration (Hosmer-Lemeshow goodness of fit test, p = 0.070). Moreover, an RV/LV ratio > 1.165 was predictive of adverse outcomes with sensitivity and specificity of 88.00 and 59.20%, respectively. The WBC counts were also able to predict adverse outcomes (AUC = 0.752, p < 0.01) and calibration (Hosmer-Lemeshow goodness of fit test, p = 0.251). A WBC count > 9.05 was predictive of adverse outcomes with sensitivity and specificity of 68.00 and 73.50%, respectively. CONCLUSION: Overall, a SaO2 < 90%, RV/LV ratio, Syncope, NTW in V1-V3, and WBC counts could independently predict adverse outcomes in hospitalized intermediate-risk APE patients.


Assuntos
Embolia Pulmonar , Disfunção Ventricular Direita , Doença Aguda , Arritmias Cardíacas , Humanos , Valor Preditivo dos Testes , Prognóstico , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/terapia , Estudos Retrospectivos , Síncope
5.
BMC Cardiovasc Disord ; 20(1): 482, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176705

RESUMO

BACKGROUND: Lung tumor embolization leading to acute myocardial infarction (AMI) is rare. Previouscases of lung tumor embolization were reported in the coronary artery. We describe here a case of lung tumor embolization leading to the simultaneous occurrence of AMI and lower extremity arterial embolism. CASE PRESENTATION: A 64-year-old patient was admitted to the emergency department complaining of chest pain and was diagnosed with AMI.An echocardiography showed a mass in the left atrium that was speculated to be a myxoma. An emergency coronary angiography found no evidence of atherosclerosis. On the second day of admission, the patient was diagnosed with lower extremity arterial embolism. Initially, we speculated that the left atrium myxoma caused an embolism resulting in the AMI and lower extremity arterial embolism.However, a lung tumor was the real cause of both conditions. Unfortunately, the patient abandoned treatment when he learned of his disease and died three days later after being discharged from the hospital. CONCLUSIONS: Lung tumor embolism is an extremely rare cause of AMI. Even rarer is the case presented here, in which a lung tumor embolism caused AMI and lower extremity arterial embolism. Clinicians should recognize lung tumor embolism as a potential cause of AMI.


Assuntos
Embolia/etiologia , Extremidade Inferior/irrigação sanguínea , Neoplasias Pulmonares/complicações , Infarto do Miocárdio/etiologia , Células Neoplásicas Circulantes/patologia , Embolia/diagnóstico por imagem , Embolia/patologia , Evolução Fatal , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , Recusa do Paciente ao Tratamento
6.
Open Life Sci ; 19(1): 20220830, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38465332

RESUMO

The pheochromocytoma is an uncommon endocrine neoplasm that originates from chromaffin cells and causes significant cardiovascular effects through the intermittent or sustained release of catecholamines. In this report, we present a rare case of myocardial infarction (MI) induced by pheochromocytoma. A 53-year-old female presented to the emergency department with a history of intermittent palpitations, back pain, and sweating for over 10 years, which had worsened over the past 2 days. The patient's cardiac enzymes and troponin levels were significantly elevated, and the electrocardiogram (ECG) showed ST-segment elevation, leading to an initial diagnosis of acute myocardial infarction. Echocardiography revealed apical ballooning, indicative of stress cardiomyopathy. Emergency coronary angiography revealed no significant stenosis, and the patient's blood pressure was fluctuating. Computerized tomography (CT) scan of the adrenal gland revealed a bilateral adrenal mass, with the left adrenal mass being larger in size after contrast-enhanced CT scan. The patient's left adrenal gland was successfully removed through laparoscopic adrenalectomy, and histopathology results confirmed the presence of adrenal pheochromocytoma. Follow-up for 3 months after discharge showed the patient had no symptoms and good prognosis. The abnormal findings on echocardiography and ECG resolved. Prompt diagnosis and management of pheochromocytoma are crucial for a favorable prognosis.

7.
J Med Case Rep ; 17(1): 295, 2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37403187

RESUMO

BACKGROUND: As a life-threatening and serious condition, aortic dissection (AD) is divided into type A and B according to its association with the ascending or descending aorta. Type A AD is often accompanied by aortic regurgitation, while type B dissections are rarely accompanied by severe aortic regurgitation. CASE PRESENTATION: We present a 71 year-old Chinese man with a rare case of type B AD with severe aortic insufficiency, who self-healed after 1 year of an aortic valve replacement. He complained of chest tightness and abdominal pain. Due to poor cardiac function, he underwent aortic valve replacement before intervening on the dissection. The operation was successful, and the dissection was treated conservatively. During the 1-year follow-up, his chest tightness improved, and the type B dissection was healed. His general condition is considerably improved. CONCLUSIONS: In type B AD combined with severe aortic insufficiency, aortic valve replacement should be prioritized. This is potentially explained by the aortic root activity and pulse pressure difference.


Assuntos
Aneurisma Aórtico , Dissecção Aórtica , Insuficiência da Valva Aórtica , Masculino , Humanos , Idoso , Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/cirurgia , Dissecção Aórtica/cirurgia , Aorta
8.
Front Cardiovasc Med ; 10: 1277528, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37840951

RESUMO

Introduction: Permanent pacemaker implantation (PPI) is a known complication in patients with aortic stenosis following transcatheter aortic valve implantation (TAVI). However, there is limited research on TAVI for pure aortic regurgitation (PAR), and more investigation is needed to determine the occurrence of postoperative cardiac conduction block and the need for PPI in this population. Therefore, this retrospective analysis aimed to evaluate the incidence of cardiac conduction block and the necessity of PPI after TAVI in patients with different types of aortic valve disease, including pure aortic stenosis (PAS), aortic stenosis with regurgitation (ASR), and PAR. Methods: Clinical data of 100 patients who TAVI were analyzed retrospectively. The incidence of conduction block was assessed, and clinical factors were examined to predict the necessity of PPI. Results: Cardiac conduction block was found to be a common complication following TAVI, particularly in patients with PAR. PAR was identified as an independent risk factor for requiring PPI. Additionally, first-degree atrioventricular block emerged as a sensitive predictor for PPI in patients with PAR. Discussion: These findings provide valuable insights into the safety and effectiveness of TAVI, which can help enhance patient management and reduce complications.

9.
Cell Signal ; 98: 110419, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35905868

RESUMO

Intraplaque hemorrhage (IPH) accelerates atherosclerosis progression. To scavenge excessive red blood cells (RBCs), vascular smooth muscle cells (VSMCs) with great plasticity may function as phagocytes. Here, we investigated the erythrophagocytosis function of VSMCs and possible regulations involved. Based on transcriptional microarray analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that genes up-regulated in human carotid atheroma with IPH were enriched in functions of phagocytic activities, while those down-regulated were enriched in VSMCs contraction function. Transcriptional expression of Milk fat globule-epidermal growth factor 8 (MFG-E8) was also down-regulated in atheroma with IPH. In high-fat diet-fed apolipoprotein E-deficient mice, erythrocytes were present in cells expressing VSMC markers αSMA in the brachiocephalic artery, suggesting VSMCs play a role in erythrophagocytosis. Using immunofluorescence and flow cytometry, we also found that eryptotic RBCs were bound to and internalized by VSMCs in a phosphatidylserine/MFG-E8/integrin αVß3 dependent manner in vitro. Inhibiting S1PR2 signaling with specific inhibitor JTE-013 or siRNA decreased Mfge8 expression and impaired the erythrophagocytosis of VSMCs in vitro. Partial ligation was performed in the left common carotid artery (LCA) followed by intra-intimal injection of isolated erythrocytes to observe their clearance in vivo. Interfering S1PR2 expression in VSMCs with Adeno-associated virus 9 inhibited MFG-E8 expression inside LCA plaques receiving RBCs injection and attenuated erythrocytes clearance. Erythrophagocytosis by VSMCs increased vascular endothelial growth factor-a secretion and promoted angiogenesis. The present study revealed that VSMCs act as phagocytes for RBC clearance through S1PR2 activation induced MFG-E8 release.


Assuntos
Músculo Liso Vascular , Placa Aterosclerótica , Animais , Eritrócitos , Fator VIII/metabolismo , Glicolipídeos , Glicoproteínas , Hemorragia/metabolismo , Humanos , Gotículas Lipídicas , Camundongos , Músculo Liso Vascular/metabolismo , Placa Aterosclerótica/metabolismo , Receptores de Esfingosina-1-Fosfato , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
Ann Clin Biochem ; 57(6): 420-428, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32936670

RESUMO

BACKGROUND: To date, the difference in microRNA expression profiles in tears of dry eye patients and healthy people has not been reported. In current study, we evaluated the significance of microRNAs and transforming growth factor beta2 (TGF-ß2) in distinguishing dry eye. METHODS: A total of 138 patients with dry eye from October 2017 to October 2018 were selected. During the same period, 138 healthy persons were collected. All patients were followed up for 12 months through outpatient, telephone or medical records and the time of corneal injury was recorded. RESULTS: Compared with healthy people, TGF-ß2 concentrations in dry eye patients were significantly decreased (P < 0.05). Array analysis, predictive software and dual-luciferase reporter assays showed that miR-450b-5p, miR-1283 and miR-3671 can target TGF-ß2 expression. Tear miR-450b-5p, miR-1283 and miR-3671 concentrations were significantly higher in dry eye patients than healthy people. A logistic regression model combining miR-450b-5p, miR-1283, miR-3671 and TGF-ß2 was performed. This model presented a high discriminating value (AUC: 0.907, 0.876-0.939, P < 0.001) than any single indicator, and the sensitivity and specificity were 77.7% and 92.7%, respectively. Compared with the low miR-450b-5p, low miR-1283, low miR-3671 and high TGF-ß2 groups, the high miR-450b-5p, high miR-1283, high miR-3671 and low TGF-ß2 groups had a significantly higher probability of corneal injury (TGF-ß2: χ2 = 5.762, P = 0.016; miR-450b-5p: χ2 = 13.267, P < 0.001; miR-1283: χ2 = 19.431, P < 0.001; miR-3671: χ2 = 8.131, P = 0.004). CONCLUSION: Current model combining tear miR-450b-5p, miR-1283, miR-3671 and TGF-ß2 had important values in the identification of dry eye and was of great value in evaluating the risk of corneal injury.


Assuntos
Síndromes do Olho Seco/metabolismo , Regulação da Expressão Gênica , MicroRNAs/biossíntese , Lágrimas/metabolismo , Fator de Crescimento Transformador beta2/biossíntese , Adulto , Idoso , Síndromes do Olho Seco/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade
11.
Mol Med Rep ; 21(6): 2580-2588, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32323830

RESUMO

Low shear stress serves an important role in the initiation and progression of atherosclerotic lesions, with an impact on progression, but its detailed mechanisms are .not yet fully known. The present study aimed to investigate endothelial cell (EC) apoptosis, as well as monocyte adhesion induced by low shear stress and the potential underlying mechanisms. The expression of platelet endothelial cell adhesion molecule­1 (PECAM­1) was demonstrated to be enhanced in human umbilical vascular ECs with a trend that was associated with time when stimulated by low shear stress compared with unstimulated cells. EC apoptosis was increased under low shear stress compared with unstimulated cells, and knockdown of PECAM­1 inhibited this process. Furthermore, downregulation of PECAM­1 reduced monocyte adhesion induced by low shear stress compared with that in the negative control cells. Mechanistically, PECAM­1 small interfering RNA transfection increased Akt and forkhead box O1 phosphorylation under low shear stress conditions compared with that in the negative control cells. Collectively, the findings of the present study revealed that low shear stress induced EC apoptosis and monocyte adhesion by upregulating PECAM­1 expression, which suggested that PECAM­1 may be a potential therapeutic target for atherosclerosis.


Assuntos
Apoptose , Adesão Celular/fisiologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Resistência ao Cisalhamento , Linhagem Celular , Técnicas de Cocultura , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Proteína Forkhead Box O1/metabolismo , Humanos , Monócitos/citologia , Monócitos/metabolismo , Fosforilação , Molécula-1 de Adesão Celular Endotelial a Plaquetas/antagonistas & inibidores , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo
12.
Life Sci ; 256: 117886, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32497631

RESUMO

AIMS: Reactive oxygen species (ROS) caused by high glucose (HG) is involved in a lot of diseases including diabetes. However, the underlying mechanism of ROS induction by HG remains unclear. Emerging evidence has shown the 8-oxoguanine glycosylase (OGG1) is the main DNA glycosylase responsible for atherosclerosis, obesity, hepatic steatosis, and insulin resistance, and so on. Our aim was to explore the role of OGG1 on HG-mediated endothelial ROS. MAIN METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to HG (30 mM) for different time periods. HG predominantly inhibited OGG1 expression in a time-dependent manner measured by western blotting, qPCR and immunofluorescence. Additionally, HUVECs were cultured with a fluorescent probe, DCFH and DHE, after being subjected to HG. Cell chemiluminescence and flow cytometry results revealed that HG caused endothelial ROS activation. KEY FINDINGS: High glucose remarkably decreased endothelial OGG1 expression. The overexpression of OGG1 significantly reversed HG-mediated PKC and NADPH oxidase activities and ROS levels. Moreover, manipulated expression of PKC significantly contacted the role of OGG1 on NADPH oxidase activation. SIGNIFICANCE: These results suggest that OGG1 downregulation promoted HG-induced endothelial ROS production and might be a potential clinical treatment target of diabetics.


Assuntos
DNA Glicosilases/metabolismo , Glucose/toxicidade , Células Endoteliais da Veia Umbilical Humana/metabolismo , NADPH Oxidases/metabolismo , Proteína Quinase C/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Animais , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Camundongos , Modelos Biológicos , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
13.
Life Sci ; 224: 212-221, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30914314

RESUMO

BACKGROUND: Oscillatory shear stress (OSS) occurs in areas where atherosclerosis is prevalent. Toll-like receptor 2 (TLR2) has been associated with mechanical-stress-mediated activation of signalling pathways that may lead to inflammation, apoptosis, and atherosclerosis. Nonetheless, the mechanism underlying the connection between TLR2 and OSS is not fully understood. The purpose of this study was to investigate the link between OSS and TLR2 in human umbilical vein endothelial cell (HUVECs). METHODS: Monolayer endothelial cells were stimulated or not stimulated by OSS. Protein expression was determined by western blotting and immunofluorescent staining. Endothelial function was assessed by using dihydroethidium assay, RT-PCR, immunofluorescent staining and western blotting. The carotid artery of rats was ligated for 1 week, and a section exposed to OSS was excised and analysed. RESULTS: In vitro, the expression of TLR2 in HUVECs was activated by OSS. Additionally, OSS increased apoptosis, inflammatory changes, and oxidative stress in HUVECs, and these effects were reversed by down-regulation the expression of TLR2. We proved that OSS regulates the inflammatory response of endothelial cells through the TLR2-TAK1-IKK2 pathway. In the rats with carotid artery ligation, TLR2, TAK1 and phospho-IKK2 amounts increased at the site of OSS. SIGNIFICANCE: According to our results, the OSS-mediated HUVECs injury may be associated with an increase in TLR2 expression. Accordingly, strategies designed to reduce TLR2 expression or inhibit TLR2 activation may be an effective approach to reduce the incidence of atherosclerosis.


Assuntos
Quinase I-kappa B/metabolismo , Inflamação/patologia , MAP Quinase Quinase Quinases/metabolismo , Estresse Oxidativo , Estresse Mecânico , Receptor 2 Toll-Like/metabolismo , Animais , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana , Humanos , Quinase I-kappa B/genética , Inflamação/etiologia , Inflamação/metabolismo , MAP Quinase Quinase Quinases/genética , Ratos , Ratos Sprague-Dawley , Resistência ao Cisalhamento , Receptor 2 Toll-Like/genética
14.
Eur J Pharmacol ; 856: 172413, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31152700

RESUMO

A characteristic of endothelia damage and repair is the turnover of extracellular matrix components. As a part of extracellular matrix glycosaminoglycan (GAG), hyaluronic acid (HA, main component of glycocalyx) is not only involved in inflammation, proliferation, differentiation of cells, and tissue remodeling, but also functions as a barrier of endothelium via preventing blood flow-induced injury from endothelial layer. Therefore, the metabolism of hyaluronic acid could allow the fine-tuning of cell behavior. In this study, we found that low shear stress decreased the expression of hyaluronic acid, whereas pretreatment with berberine could significantly increase the expression of hyaluronic acid in vitro and in vivo. On this background, it is very important to better understand the beneficial effect of berberine (BBR) on low shear stress-induced degradation of hyaluronic acid and its potential mechanism. By using siRNA and inhibitors, we testified that AMP-activated protein kinase (AMPK) and p47phox/hyaluronidase 2 (Hyal2) signaling pathway involved in the modulation of hyaluronic acid metabolism. Further, berberine, by increasing AMPK phosphorylation, decreased the dissociation of p47phox/Hyal2, and subsequently inhibited Hyal2 activation and p47phox phosphorylation, leading to the metabolic maintaining of hyaluronic acid. Importantly, we primarily demonstrated a direct binding between AMPKα and p47phox in HUVECs by co-immunoprecipitation. On the other hand, berberine also increased the expression of hyaluronic acid synthase 2 (HAS2) by regulating AMPKα/p47phox signaling pathway. Taken together, berberine treatment can attenuate low shear stress-induced hyaluronic acid degradation via increasing phosphorylation of AMPKa, and then not only downregulates p47phox and Hyal2 activity but also upregulates the expression of HAS2.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Berberina/farmacologia , Moléculas de Adesão Celular/metabolismo , Glicocálix/metabolismo , Hialuronoglucosaminidase/metabolismo , NADPH Oxidases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estresse Mecânico , Animais , Fenômenos Biomecânicos/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Proteínas Ligadas por GPI/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Glicocálix/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Ácido Hialurônico/metabolismo , Camundongos , Fosforilação/efeitos dos fármacos
15.
Colloids Surf B Biointerfaces ; 129: 63-70, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25829128

RESUMO

Self-assembled core/shell nanoparticles (NPs) were synthesized from water-soluble alginate substituted by hydrophobic phytosterols. Folate, a cancer-cell-specific ligand, was conjugated to the phytosterol-alginate (PA) NPs for targeting folate-receptor-overexpressing cancer cells. The physicochemical properties of folate-phytosterol-alginate (FPA) NPs were characterized by nuclear magnetic resonance, transmission electron microscopy, dynamic light scattering, electrophoretic light scattering, and fluorescence spectroscopy. Doxorubicin (DOX), an anticancer drug, was entrapped inside prepared NPs by dialysis method. The identification of prepared FPA NPs to folate-receptor-overexpressing cancer cells (KB cells) was confirmed by cytotoxicity and folate competition assays. Compared to the pure DOX and DOX/PA NPs, the DOX/FPA NPs had lower IC50 value to KB cells because of folate-receptor-mediated endocytosis process and the cytotoxicity of DOX/FPA NPs to KB cells could be competitively inhibited by free folate. The cellular uptake and internalization of pure DOX and DOX/FPA NPs was confirmed by confocal laser scanning microscopy image and the higher intracellular uptake of drug for DOX/FPA NPs over pure DOX was observed. The FPA NPs had the potential as a promising carrier to target drugs to cancer cells overexpressing folate receptors and avoid cytotoxicity to normal tissues.


Assuntos
Alginatos/química , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Ácido Fólico/química , Nanopartículas/química , Fitosteróis/química , Antibióticos Antineoplásicos/farmacologia , Portadores de Fármacos , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Células KB , Microscopia Eletrônica de Transmissão , Tamanho da Partícula
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