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1.
J Coll Physicians Surg Pak ; 34(4): 468-473, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38576292

RESUMO

OBJECTIVE: To determine the link between heart rate variability (HRV) and short-term adverse outcomes (re-hospitalisation or death due to cardiac arrhythmia, recurrent myocardial infarction, heart failure, all-cause death) in acute myocardial infarction (AMI). STUDY DESIGN: A descriptive study. Place and Duration of the Study: Department of Cardiovascular Medicine, The First Affiliated Hospital of Anhui Medical University, China, from January 2018 to December 2021. METHODOLOGY: Clinical data of 245 patients diagnosed with AMI were retrospectively analysed. After discharge from the hospital, patients were followed for a year and categorised into two groups based on the occurrence of adverse events: the adverse event group (n=82) and the no adverse event group (n=163). Differences in clinical characteristics were compared, independent factors influencing adverse events were analysed, and diagnostic efficacy was assessed. RESULTS: Univariate analysis showed age, hyperlipidaemia, specific HRV parameters (SDNN, SDANN, RMSSD, PNN50, LF/HF), and myocardial injury markers (CK-MB, cTnI, NT-proBNP) as associated with these events (all p < 0.05). Multivariable analysis revealed decreased SDNN, decreased SDANN, increased LF/HF, and elevated levels of CK-MB, cTnI, and NT-proBNP as independent influences. Both HRV parameters and myocardial injury markers were reliable predictors on ROC curve analysis. The highest diagnostic efficacy was achieved by combining these predictors. CONCLUSION: AMI patients frequently experience short-term adverse events. Both HRV parameters and myocardial injury markers, which demonstrate significant predictive efficacy, independently influence these outcomes. KEY WORDS: Acute myocardial infarction, Coronary angiography, Heart rate variability, Myocardial injury, Risk factors.


Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Humanos , Frequência Cardíaca/fisiologia , Estudos Retrospectivos , Infarto do Miocárdio/diagnóstico , Prognóstico
2.
Environ Res ; 214(Pt 4): 114085, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35987376

RESUMO

Cesium (Cs) is a byproduct of nuclear bombs, nuclear weapons testing, and nuclear fission in nuclear reactors. Cs can enter the human body through food or air and cause lasting damage. Highly efficient and selective removal of 137Cs from low-level radioactive effluents (LLREs), which contain many radionuclides and dissolved heavy metal species, is imperative for minimizing LLRE volume, and facilitating their final disposal. Prussian blue analogs (PBAs) have received much attention as materials for the removal of radioactive Cs because of their affinity for adsorbing Cs+. In this study, an inexpensive and readily available cyanide-based functional material (PBACu) exhibiting high efficiency and excellent selectivity toward Cs capture was designed through a facile low-temperature co-precipitation process. Nano-PBACu, crystallizing in the cubic space group (Fm-3m (225)), has an average pore size of 6.53 nm; consequently, PBACu can offer abundant atomic occupation sites for capturing and incorporating Cs. Here, the pseudo-second-order kinetic model and Langmuir model fitted well with the adsorption of Cs + on PBACu, with a maximum capture capacity of 95.75 mg/g within 5 min, confirming that PBACu could rapidly capture Cs ions. PBACu strongly and selectively interacted with Cs even in a simulant containing large Na+, NH4+, Ca2+, and Mg2+ ion concentrations in an aqueous solution. The process of Cs + adsorption by cyanide-based functional crystals was confirmed to involve the entry of Cs+ into cyanide-based functional crystals to replace K+ and finally achieve the lattice incorporation of Cs. The current results broaden the lattice theory of radionuclide Cs removal and provide a promising alternative for the immobilization of Cs from radioactive wastewater.


Assuntos
Césio , Cianetos , Adsorção , Césio/química , Humanos , Concentração de Íons de Hidrogênio , Águas Residuárias/química
3.
Comput Math Methods Med ; 2022: 3684700, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35345521

RESUMO

Objective: Coronary heart disease (CHD) is considered an inflammatory relative disease. This study is aimed at analyzing the health information of serum interferon in CHD based on logistic regression and artificial neural network (ANN) model. Method: A total of 155 CHD patients diagnosed by coronary angiography in our department from January 2017 to March 2020 were included. All patients were randomly divided into a training set (n = 108) and a test set (n = 47). Logistic regression and ANN models were constructed using the training set data. The predictive factors of coronary artery stenosis were screened, and the predictive effect of the model was evaluated by using the test set data. All the health information of participants was collected. Expressions of serum IFN-γ, MIG, and IP-10 were detected by double antibody sandwich ELISA. Spearman linear correlation analysis determined the relationship between the interferon and degree of stenosis. The logistic regression model was used to evaluate independent risk factors of CHD. Result: The Spearman correlation analysis showed that the degree of stenosis was positively correlated with serum IFN-γ, MIG, and IP-10 levels. The logistic regression analysis and ANN model showed that the MIG and IP-10 were independent predictors of Gensini score: MIG (95% CI: 0.876~0.934, P < 0.001) and IP-10 (95% CI: 1.009~1.039, P < 0.001). There was no statistically significant difference between the logistic regression and the ANN model (P > 0.05). Conclusion: The logistic regression model and ANN model have similar predictive performance for coronary artery stenosis risk factors in patients with CHD. In patients with CHD, the expression levels of IFN-γ, IP-10, and MIG are positively correlated with the degree of stenosis. The IP-10 and MIG are independent risk factors for coronary artery stenosis.


Assuntos
Estenose Coronária , Constrição Patológica , Angiografia Coronária , Estenose Coronária/diagnóstico por imagem , Humanos , Modelos Logísticos , Redes Neurais de Computação
4.
J Hazard Mater ; 424(Pt A): 127208, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34592591

RESUMO

Halloysite nanotubes (HNTs) are considered structurally promising adsorption materials, but their application is limited due to their poor native adsorption properties. Improving the adsorption capacity of HNTs for radioactive U(VI) is of great significance. By controlling the mass ratio of HNTs and dopamine (DA), composite adsorbents (HNTs@PDA) with different polydopamine (PDA) layer thicknesses were synthesized. Characterization of HNTs@PDA demonstrated that the original structure of the HNTs was maintained. Adsorption experiments verified that the adsorption capacity of HNTs@PDA for U(VI) was significantly improved. The effects of solution pH, temperature, and coexisting ions on the adsorption process were investigated. The removal efficiency was observed to be 75% after five repeated uses. The adsorption mechanism of U(VI) by HNTs@PDA can be explained by considering electrostatic interactions and the complexation of C-O, -NH- and C-N/CN in the PDA layer. This study provides some basic information for the application of HNTs for U(VI) removal.


Assuntos
Nanotubos , Urânio , Argila , Indóis , Polímeros
5.
Ann Palliat Med ; 10(10): 10887-10895, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34763450

RESUMO

BACKGROUND: Heart failure (HF) often complicates atrial fibrillation (AF) and conversely, AF frequently complicates HF. Furthermore, the coexistence of both conditions significantly increases the risk of cardiovascular complications. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been demonstrated to decrease hospitalizations for HF and reduce cardiovascular death. Therefore, this study evaluated the effects of SGLT-2 inhibitors on AF in patients with HF. METHODS: A total of 903 patients with HF were enrolled in this study. Basic patient data including demographic characteristics, medical history, cardiovascular medications, and results of biochemical tests were collated. Logistic regression analysis was performed to examine the association between SGLT-2 inhibitors and the risk of AF. The effects of SGLT-2 inhibitors on AF were further analyzed according to subgroups. RESULTS: Patients treated with SGLT-2 inhibitors experienced a lower prevalence of AF (8.4% vs. 12.1%, P<0.001) compared to patients without SGLT-2 treatment. Controlling for potential confounders revealed that SGLT-2 inhibitors decreased the risk of AF by 24% [odds ratio (OR): 0.76; 95% confidence interval (CI): 0.70-0.85; P<0.001]. The effect of SGLT-2 inhibitors on AF was consistent in patients aged < 65 years and patients aged ≥65 years (OR =0.82 and 95% CI: 0.71-0.88 vs. OR =0.84 and 95% CI: 0.77-0.92, respectively; P interaction =0.501). Similarly, neither gender, body mass index (BMI), estimated glomerular filtration rate (eGFR), nor the New York Heart Association (NYHA) classification affected the protective effect of SGLT-2 inhibitors. CONCLUSIONS: SGLT-2 inhibitors reduced the risk of AF in patients with HF, and the effect was consistent irrespective of age, gender, BMI, eGFR, and NYHA classification.


Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Fibrilação Atrial/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/prevenção & controle , Fatores de Risco , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
6.
Medicine (Baltimore) ; 96(17): e6647, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28445265

RESUMO

Diabetes mellitus (DM) has been proved to be a predictor of adverse outcomes after percutaneous coronary intervention (PCI). Drug-eluting stents (DESs) could reduce the adverse events in DM patients. In this study, we aimed to analyze the clinical outcome after DES implantation in diabetic versus nondiabetic patients in China. Totally, 200 Chinese DM patients and 400 Chinese non-DM patients were enrolled in this retrospective study. Compared with non-DM patients, DM patients were more likely to have a higher incidence of cardiac death (3.5% vs. 1.0%, P = .048), stent thrombosis (2.5% vs. 0.5%, P = .044), target lesion revascularization (6.0% vs. 1.8%, P = .005), target vessel failure (15.5% vs. 8.0%, P < .001), target lesion failure (14.0% vs. 4.3%, P < .001), myocardial infarction (4.5% vs. 1.5%, P = .030), and major adverse cardiac events (12.5% vs. 5.0%, P = .001) at 2-year follow-up. However, the incidence of target vessel revascularization (7.5% vs. 5.5%, P = .340) was similar between DB and non-DB patients. Patients with DB (hazard ratio [HR] = 2.54, P = .001), older than 80 years (HR = 1.33, P = .027) with hypercholesterolemia (HR = 1.03, P < .001), serum creatinine >177 µmol/L (HR = 3.04, P = .011), a history of cerebral vascular accident (HR = 4.29, P = .010), or a history of myocardial infarction (HR = 31.4, P < .001) were more likely to experience adverse events. In China, DM could also be served as an independent predictor of adverse outcomes after DES implantation. These patients should be reexamined more frequently.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/cirurgia , Complicações do Diabetes , Stents Farmacológicos/efeitos adversos , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/mortalidade , Idoso , China , Doença Crônica , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Intervenção Coronária Percutânea/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
7.
Stud Health Technol Inform ; 245: 118-121, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29295064

RESUMO

Lorenz plot (LP) method gives a global view of long-time electrocardiogram signals, is an efficient simple visualization tool to analyze heart rate variability and cardiac arrhythmias. 50 records of RR-interval time series with frequent premature complexes exported from 24-hour Holter. Constructed three-dimensional LP (3DLP) with three successive RR intervals as X, Y and Z axis in Cartesian coordinate system for each record, then stereographic projection it along the space diagonal. The radii of dots distinguished eccentric clusters (ECs) points from centric clusters' with the accuracy of 94 ± 6.0%. The eccentric scatter-dots were separated and identified by the frequency distribution characteristic on azimuth, with the accuracy of 93 ± 13.3% ECs. The APF < -2.8° of CPN EC supported the ventricular extrasystoles diagnosis, with excellent sensitivity (1.0) and specificity (0.92). The transformed coordinates (polar radius and angle) of 3DLP could extract and quantify clusters to diagnose arrhythmia, and might provide additional prognosis information.


Assuntos
Arritmias Cardíacas , Eletrocardiografia , Eletrocardiografia Ambulatorial , Previsões , Frequência Cardíaca , Humanos , Sensibilidade e Especificidade , Estatística como Assunto
8.
Lipids Health Dis ; 13: 115, 2014 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-25028180

RESUMO

BACKGROUND: Rho kinase over-activation is associated with nitric oxide (NO) reduction and atherosclerosis. Metformin is favorable for endothelial function improvement and cardiovascular outcomes. Whether cardio-protective effect of metformin is associated with Rho kinase activity is unknown. METHODS: Hyperlipidemia model of rats were established accordingly. Thereafter, medical interventions in terms of atorvastatin, metformin or combined therapy were administered for 4 weeks. Laboratory parameters were compared among each groups at initial, 6 weeks of high-fat and high-cholesterol diet administration, and 4 weeks of medical intervention. Lineal regression analyses were performed. RESULTS: No significant difference of laboratory parameters was observed initially. Six weeks of high-fat and high-cholesterol diet administration, serum levels of cholesterol, C-reactive protein (CRP) level, and Rho kinase activity were significantly increased while NO production was concomitantly reduced in comparison to the sham group. After 4 weeks of medical intervention, CRP level and Rho kinase activity were profoundly diminished while NO production was significantly enhanced in the atorvastatin and metformin groups, and these benefits were further enhanced with combined therapy. Lineal regression analyses showed that Rho kinase activity was negatively correlated with NO production but positively correlated with CRP level. CONCLUSION: In rats with hyperlipidemia, metformin and atorvastatin therapy is favorable for NO production and CRP reduction, which might be associated with Rho kinase activity decrease.


Assuntos
Anticolesterolemiantes/farmacologia , Ácidos Heptanoicos/farmacologia , Hipercolesterolemia/tratamento farmacológico , Metformina/farmacologia , Óxido Nítrico/biossíntese , Pirróis/farmacologia , Quinases Associadas a rho/sangue , Animais , Anticolesterolemiantes/uso terapêutico , Atorvastatina , Proteína C-Reativa/metabolismo , Avaliação Pré-Clínica de Medicamentos , Ácidos Heptanoicos/uso terapêutico , Hipercolesterolemia/sangue , Hipercolesterolemia/enzimologia , Masculino , Metformina/uso terapêutico , Óxido Nítrico/sangue , Pirróis/uso terapêutico , Ratos Sprague-Dawley
9.
Redox Biol ; 2: 570-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24688893

RESUMO

NADPH oxidases are the major sources of reactive oxygen species in cardiovascular, neural, and kidney cells. The NADPH oxidase 5 (NOX5) gene is present in humans but not rodents. Because Nox isoforms in renal proximal tubules (RPTs) are involved in the pathogenesis of hypertension, we tested the hypothesis that NOX5 is differentially expressed in RPT cells from normotensive (NT) and hypertensive subjects (HT). We found that NOX5 mRNA, total NOX5 protein, and apical membrane NOX5 protein were 4.2±0.7-fold, 5.2±0.7-fold, and 2.8±0.5-fold greater in HT than NT. Basal total NADPH oxidase activity was 4.5±0.2-fold and basal NOX5 activity in NOX5 immunoprecipitates was 6.2±0.2-fold greater in HT than NT (P=<0.001, n=6-14/group). Ionomycin increased total NOX and NOX5 activities in RPT cells from HT (P<0.01, n=4, ANOVA), effects that were abrogated by pre-treatment of the RPT cells with diphenylene-iodonium or superoxide dismutase. Silencing NOX5 using NOX5-siRNA decreased NADPH oxidase activity (-45.1±3.2% vs. mock-siRNA, n=6-8) in HT. D1-like receptor stimulation decreased NADPH oxidase activity to a greater extent in NT (-32.5±1.8%) than HT (-14.8±1.8). In contrast to the marked increase in expression and activity of NOX5 in HT, NOX1 mRNA and protein were minimally increased in HT, relative to NT; total NOX2 and NOX4 proteins were not different between HT and NT, while the increase in apical RPT cell membrane NOX1, NOX2, and NOX4 proteins in HT, relative to NT, was much less than those observed with NOX5. Thus, we demonstrate, for the first time, that NOX5 is expressed in human RPT cells and to greater extent than the other Nox isoforms in HT than NT. We suggest that the increased expression of NOX5, which may be responsible for the increased oxidative stress in RPT cells in human essential hypertension, is caused, in part, by a defective renal dopaminergic system.


Assuntos
Hipertensão/enzimologia , Túbulos Renais Proximais/enzimologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Células Cultivadas , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Ionomicina/farmacologia , Isoenzimas/genética , Isoenzimas/metabolismo , Túbulos Renais Proximais/citologia , NADPH Oxidase 5 , Oniocompostos/farmacologia , Estresse Oxidativo
10.
Hypertens Res ; 36(4): 334-41, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23324866

RESUMO

The cardio-ankle vascular index (CAVI) has been widely accepted as a good indicator of arteriosclerosis. However, the lack of a reliable diagnostic criterion for CAVI hampers the proper clinical screening for arteriosclerosis using CAVI and impedes the prompt treatment of cardiovascular disease (CVD). There is an urgent need to determine a criterion for CAVI in arteriosclerosis prevention. We conducted a cross-sectional study to determine this criterion based on receiver operating characteristic (ROC) analyses in a Chinese population consisting of 328 participants. CAVI was measured in duplicate, and carotid ultrasound detection was performed in a quiet environment by well-trained physicians. After multivariate adjustment, CAVI was positively associated with the risk of carotid arteriosclerosis. Compared with participants in the lowest tertile of CAVI (5.15-7.40), those in the medium (7.41-8.65) and highest (8.66-13.60) tertiles had odds ratios (95% confidence interval) of 2.2 (1.0, 4.9) and 4.4 (1.5, 13.3), respectively, for developing carotid arteriosclerosis (P trend=0.007). The areas under the ROC curve (AUC) of the male, female and pooled populations were 0.789, 0.897 and 0.856, respectively. The cutoff point of CAVI≥8.0 resulted in the largest sensitivity and specificity. Furthermore, CAVI and age acted synergistically to increase the risk of carotid arteriosclerosis. CAVI≥8.0 may be an optimal cutoff point for carotid arteriosclerosis prediction. The older population with higher CAVI scores had a higher risk of carotid arteriosclerosis. Additional large prospective studies are needed to confirm our findings.


Assuntos
Tornozelo/irrigação sanguínea , Doenças das Artérias Carótidas/fisiopatologia , Rigidez Vascular/fisiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Povo Asiático , Velocidade do Fluxo Sanguíneo , Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico , Doenças das Artérias Carótidas/diagnóstico por imagem , Estudos Transversais , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/patologia , Valor Preditivo dos Testes , Curva ROC , Valores de Referência , Fatores de Risco , Fatores Socioeconômicos , Ultrassonografia , Adulto Jovem
11.
Free Radic Biol Med ; 50(7): 832-40, 2011 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-21193028

RESUMO

Dopamine cellular signaling via the D(1) receptor (D(1)R) involves both protein kinase A (PKA) and protein kinase C (PKC), but the PKC isoform involved has not been determined. Therefore, we tested the hypothesis that the D(1)R-mediated inhibition of NADPH oxidase activity involves cross talk between PKA and a specific PKC isoform(s). In HEK-293 cells heterologously expressing human D(1)R (HEK-hD(1)), fenoldopam, a D(1)R agonist, and phorbol 12-myristate 13-acetate (PMA), a PKC activator, inhibited oxidase activity in a time- and concentration-dependent manner. The D(1)R-mediated inhibition of oxidase activity (68.1±3.6%) was attenuated by two PKA inhibitors, H89 (10µmol/L; 88±8.1%) and Rp-cAMP (10µmol/L; 97.7±6.7%), and two PKC inhibitors, bisindolylmaleimide I (1µmol/L; 94±6%) and staurosporine (10nmol/L; 93±8%), which by themselves had no effect (n=4-8/group). The inhibitory effect of PMA (1µmol/L) on oxidase activity (73±3.2%) was blocked by H89 (100±7.8%; n=5 or 6/group). The PMA-mediated inhibition of NADPH oxidase activity was accompanied by an increase in PKCθ(S676), an effect that was also blocked by H89. Fenoldopam (1µmol/L) also increased PKCθ(S676) in HEK-hD(1) and human renal proximal tubule (RPT) cells. Knockdown of PKCθ with siRNA in RPT cells prevented the inhibitory effect of fenoldopam on NADPH oxidase activity. Our studies demonstrate for the first time that cross talk between PKA and PKCθ plays an important role in the D(1)R-mediated negative regulation of NADPH oxidase activity in human kidney cells.


Assuntos
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , NADPH Oxidases/antagonistas & inibidores , Proteína Quinase C/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Receptores de Dopamina D1/agonistas , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Transformada , Dopamina/metabolismo , Ativação Enzimática/efeitos dos fármacos , Fenoldopam/farmacologia , Expressão Gênica , Humanos , Rim/efeitos dos fármacos , Rim/enzimologia , NADPH Oxidases/metabolismo , Fosforilação/efeitos dos fármacos , Isoformas de Proteínas/metabolismo , Proteína Quinase C/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptores de Dopamina D1/metabolismo , Estaurosporina/farmacologia , Acetato de Tetradecanoilforbol/farmacologia
12.
Hypertension ; 53(6): 1054-61, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19380616

RESUMO

NADPH oxidase (Nox)-dependent reactive oxygen species production is implicated in the pathogenesis of cardiovascular diseases, including hypertension. We tested the hypothesis that oxidase subunits are differentially regulated in renal proximal tubules from normotensive and spontaneously hypertensive rats. Basal Nox2 and Nox4, but not Rac1, in immortalized renal proximal tubule cells and brush border membranes were greater in hypertensive than in normotensive rats. However, more Rac1 was expressed in lipid rafts in cells from hypertensive rats than in cells from normotensive rats; the converse was observed with Nox4, whereas Nox2 expression was similar. The D(1)-like receptor agonist fenoldopam decreased Nox2 and Rac1 protein in lipid rafts to a greater extent in hypertensive than in normotensive rats. Basal oxidase activity was 3-fold higher in hypertensive than in normotensive rats but was inhibited to a greater extent by fenoldopam in normotensive (58+/-3.3%) than in hypertensive rats (31+/-5.2%; P<0.05; n=6 per group). Fenoldopam decreased the amount of Nox2 that coimmunoprecipitated with p67(phox) in cells from normotensive rats. D(1)-like receptors may decrease oxidase activity by disrupting the distribution and assembly of oxidase subunits in cell membrane microdomains. The cholesterol-depleting reagent methyl-beta-cyclodextrin decreased oxidase activity and cholesterol content to a greater extent in hypertensive than in normotensive rats. The greater basal levels of Nox2 and Nox4 in cell membranes and Nox2 and Rac1 in lipid rafts in hypertensive rats than in normotensive rats may explain the increased basal oxidase activity in hypertensive rats.


Assuntos
Túbulos Renais Proximais/citologia , Microdomínios da Membrana/metabolismo , NADPH Oxidases/metabolismo , Receptores de Dopamina D1/metabolismo , Análise de Variância , Animais , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Células Cultivadas , Fenoldopam/farmacologia , Immunoblotting , Luminescência , NADPH Oxidases/genética , Probabilidade , RNA Mensageiro/análise , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Espécies Reativas de Oxigênio/metabolismo , Receptores de Dopamina D1/agonistas , Sensibilidade e Especificidade
13.
Hypertension ; 51(2): 481-7, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18195159

RESUMO

Recent studies have indicated the importance of cholesterol-rich membrane lipid rafts (LRs) in oxidative stress-induced signal transduction. Reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidases, the major sources of reactive oxygen species, are implicated in cardiovascular diseases, including hypertension. We tested the hypothesis that NADPH oxidase subunits and activity are regulated by LRs in human renal proximal tubule cells. We report that a high proportion of p22(phox) and the small GTPase Rac1 are expressed in LRs in human renal proximal tubule cells. The D(1)-like receptor agonist, fenoldopam (1 micromol/L per 20 minutes) dispersed Nox subunits within LRs and non-LRs and decreased oxidase activity (30.7+/-3.3%). In contrast, cholesterol depletion (2% methyl-beta-cyclodextrin [beta CD]) translocated NADPH oxidase subunits out of LRs and increased oxidase activity (154.0+/-10.5% versus control, 103.1+/-3.4%), which was reversed by cholesterol repletion (118.9+/-9.9%). Moreover, NADPH oxidase activation by beta CD (145.5+/-9.0%; control: 98.6+/-1.6%) was also abrogated by the NADPH oxidase inhibitors apocynin (100.4+/-3.2%) and diphenylene iodonium (9.5+/-3.3%). Furthermore, beta CD-induced reactive oxygen species production was reversed by knocking down either Nox2 (81.0+/-5.1% versus beta CD: 162.0+/-2.0%) or Nox4 (108.0+/-10.8% versus beta CD: 152.0+/-9.8%). We have demonstrated for the first time that disruption of LRs results in NADPH oxidase activation that is abolished by antioxidants and silencing of Nox2 or Nox4. Therefore, in human renal proximal tubule cells, LRs maintain NADPH oxidase in an inactive state.


Assuntos
Túbulos Renais Proximais/enzimologia , Microdomínios da Membrana/fisiologia , NADPH Oxidases/metabolismo , Acetofenonas/farmacologia , Membrana Celular/enzimologia , Colesterol/metabolismo , Agonistas de Dopamina/farmacologia , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Fenoldopam/farmacologia , Humanos , Immunoblotting , Isoenzimas/genética , Túbulos Renais Proximais/citologia , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/genética , NADPH Oxidase 2 , NADPH Oxidase 4 , NADPH Oxidases/antagonistas & inibidores , NADPH Oxidases/genética , Oniocompostos/farmacologia , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Receptores de Dopamina D1/agonistas , beta-Ciclodextrinas/farmacologia
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