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1.
Chem Commun (Camb) ; 59(9): 1217-1220, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36629537

RESUMO

A novel protocol for the synthesis of highly functionalized benzo[b][1,5]diazocin-6(5H)-one derivatives (BDCOs, 4 and 5) from 2-aryl-1H-indoles and 1,1-enediamines was developed via a complex cascade of reactions including regioselective free radical oxidation, the 1,2-addition of imine, imine-enamine tautomerization, intramolecular cyclization, and ring expansion. The cascade reaction was enabled by refluxing a mixture of two substrates in the presence of di-tert-butyl peroxide (DTBP) as an oxidant and anhydrous CuI as a catalyst in toluene under argon protection. Consequently, a series of BDCOs (4 and 5) were synthesized with high regioselectivity in good yield. This protocol can be used for the synthesis of functionalized BDCOs via a one-pot oxidative annulation reaction rather than a multi-step reaction, which is suitable for both combinatorial and parallel syntheses of BDCOs.

2.
Kaohsiung J Med Sci ; 38(2): 149-156, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34741409

RESUMO

Previous studies have demonstrated that the levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis, are strongly associated with hypertension, diabetes, and cardiovascular diseases. Profilin-1, an actin-binding protein, has been documented to be involved in endothelial injury and in the proliferation of vascular smooth muscle cells resulting from hypertension. However, the role of profilin-1 in ADMA-induced vascular injury in hypertension remains largely unknown. Forty healthy subjects and forty-two matched patients with essential hypertension were enrolled, and the related indexes of vascular injury in plasma were detected. Rat aortic smooth muscle cells (RASMCs) were treated with different concentrations of ADMA for different periods of time and transfected with profilin-1 small hairpin RNA to interrupt the expression of profilin-1. To determine the role of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway, RASMCs were pretreated with AG490 or rapamycin. The expression of profilin-1 was tested using real-time polymerase chain reaction (PCR) and western blot analysis. Cell proliferation was measured by flow cytometry and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazoliumbromide assays. Compared with healthy subjects, the levels of ADMA and profilin-1 were markedly elevated in hypertensive individuals, while the levels of NO were significantly decreased (p < 0.05). In vitro, studies showed ADMA-induced profilin-1 expression in a concentration- and time-dependent manner in RASMCs (p < 0.05), concomitantly with promoting the proliferation of RASMCs. Furthermore, ADMA-mediated proliferation of RASMCs and upregulation expression of profilin-1 were inhibited by blockade of the JAK2/STAT3 pathway or knockdown of profilin-1. Profilin-1 implicated in the ADMA-mediated vascular lesions in hypertension.


Assuntos
Arginina/análogos & derivados , Endotélio Vascular/efeitos dos fármacos , Hipertensão/etiologia , Miócitos de Músculo Liso/efeitos dos fármacos , Profilinas/fisiologia , Animais , Arginina/farmacologia , Arginina/fisiologia , Proliferação de Células , Endotélio Vascular/patologia , Humanos , Miócitos de Músculo Liso/patologia , Ratos
3.
Am J Ther ; 23(6): e1586-e1596, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25901664

RESUMO

A meta-analysis-based study was conducted to examine the clinical value of serum C-reactive protein (CRP) levels in predicting postoperative atrial fibrillation (POAF) in patients with coronary artery disease (CAD) who underwent coronary artery bypass graft. Computer-based search of scientific literature databases was performed to identify relevant studies in strict accordance with our inclusion and exclusion criteria. Data extracted from the selected studies were used to perform meta-analysis using the STATA 12.0 statistical software. Standardized mean differences (SMDs) with their 95% confidence interval (95% CI) were calculated. The database search strategy initially identified 62 articles (Chinese = 17, English = 45). After multiple levels of screening and validation, 15 case-control studies (Chinese = 1, English = 14), containing of a total of 3110 atrial fibrillation patients (POAF = 925, non-POAF = 2185), were selected for our meta-analysis. The meta-analysis results confirmed that serum CRP level was remarkably higher in patients with POAF compared with non-POAF (SMD = 1.36; 95% CI, 0.44-2.28; P = 0.004). Ethnicity-stratified analysis revealed that elevated serum CRP levels were associated with an increased risk of POAF in white patients with CAD (SMD = 0.85; 95% CI, 0.12-1.58; P = 0.022), but not Asian patients with CAD (SMD = 3.31, 95% CI, -0.04 to 6.66; P = 0.053). Elevated CRP levels, indicating profound inflammation, may be associated with significantly increased risk of POAF in patients with CAD who underwent coronary artery bypass graft. Thus, serum CRP levels are important for early diagnosis and monitoring of POAF in high-risk patients.


Assuntos
Fibrilação Atrial/epidemiologia , Proteína C-Reativa/análise , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Complicações Pós-Operatórias/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/sangue , Fibrilação Atrial/etnologia , Biomarcadores , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etnologia , Fatores de Risco
4.
Gene ; 561(2): 268-75, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25701595

RESUMO

We examined the protective role of microRNA-30b (miR-30b) in ischemia-reperfusion (I/R)-induced injury in rat H9C2 cardiomyocytes. H9C2 cells were subjected to hypoxia-reoxygenation (H/R) treatment to simulate ischemia-reperfusion (I/R) injury. H9C2 cells were divided into: vehicle control (VC) group; scrambled inhibitors (INC) group; scrambled mimics (MNC) group; H/R+VC group; H/R+INC group; H/R+mimics group. H/R induced apoptosis was detected by flow cytometry and the pathways involved in miR-30b-mediated protection were examined by analyzing the expression of miR-30b, Bcl-2, Bax, Caspase-3, KRAS, p-AKT and total AKT in H9C2 cells. Overexpression of miR-30b mimic (H/R+mimics group) significantly increased Bcl-2 and Bcl-2/Bax levels and decreased Bax and Caspase-3 levels, compared with the H/R+VC group (all P<0.05). Consistent with this, the apoptosis rate was significantly decreased in the H/R+mimics group (P<0.05) compared with the H/R+VC group. Western blot analysis revealed that overexpression of miR-30b mimic resulted in significantly increase in AKT activation and decreased KRAS, compared to the H/R+VC group (both P<0.05). In conclusion, the H/R induced apoptosis decreased miR-30b expression, but over-expression of miR-30b inhibited H/R induced apoptosis. The observed miR-30b-mediated protection against H/R induced apoptosis involved the upregulation of Ras-PI3K-Akt pathway.


Assuntos
MicroRNAs/genética , MicroRNAs/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Apoptose , Hipóxia Celular , Linhagem Celular , Regulação da Expressão Gênica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais
5.
Biomed Res Int ; 2014: 691540, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25386562

RESUMO

BACKGROUND: Fetuin-A (FA) suppresses arterial calcification, promotes insulin resistance, and appears to be elevated in patients with cardiovascular diseases (CVD), but the data is still inconsistent. To clarify the correlation between serum FA levels and the presence and severity of CVDs, we performed this meta-analysis. METHOD: Potential relevant studies were identified covering the following databases: PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases. Data from eligible studies were extracted and included in the meta-analysis using a random-effects model. RESULTS: Ten case-control studies, including 1,281 patients with CVDs and 2,663 healthy controls, were included. The results showed significant differences in serum levels of FA between the CVDs patients and the healthy controls (SMD=1.36, 95%CI: 0.37-2.36, P=0.007). Ethnicity-subgroup analysis implied that low serum FA levels are related to CVDs in Caucasians (SMD=1.73, 95%CI: 0.20-3.26, P=0.026), but not in Asians (SMD=1.04, 95%CI: -0.33-2.40, P=0.138). CONCLUSION: The data indicated that decreased serum FA level is correlated with the development of CVDs. FA might be clinically valuable for reflecting the progression of CVDs.


Assuntos
Doenças Cardiovasculares/sangue , Predisposição Genética para Doença , alfa-2-Glicoproteína-HS/metabolismo , Povo Asiático , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/patologia , China , Humanos , População Branca
6.
Chin J Integr Med ; 17(6): 414-20, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21660675

RESUMO

OBJECTIVE: To observe the effect of Chinese herbal medicine for calming Gan (肝) and suppressing hyperactive yang (平肝潜阳, CGSHY) on arterial elasticity function and the circadian rhythm of blood pressure in patients with essential hypertension (EH). METHODS: Adopting a parallel, randomized design, sixty-four patients with EH of stages I and II were randomly divided into two groups according to a random number table, with 32 in each group. The patients in the treatment group were treated with CGSHY and those in the control group were treated with Enalapril. All patients were given 24-h ambulatory blood pressure monitoring (ABPM) before and after a 12-week treatment. Trough/peak (T/P) ratios of systolic and diastolic blood pressure (SBP & DBP) of each group were calculated. The circadian rhythm of their blood pressure was observed at the same time. The changes in elasticity of the carotid artery in the patients, including stiffness parameter (ß), pressure-strain elastic modulus (Ep), arterial compliance (AC), augmentation index (AI), and pulse wave velocity (PVWß) were determined by the echo-tracking technique before and after a 12-week treatment. In the meantime, their levels of nitric oxide (NO) and endothelin-1 (ET-1) were measured respectively. RESULTS: After treatment, all parameters in the 24-h ABPM and the elasticity of the carotid artery (ß, Ep, AC and PVWß) were markedly improved, the level of NO was increased, and ET-1 was decreased in both groups as compared with values before treatment (P<0.05 or P<0.01). Further, the improvements in the ratio of T/P of SBP & DBP and in the level of NO and ET-1 in the treatment group were more significant than those in the control group (P<0.05). There were no significant differences in all parameters in the ABPM monitoring and the elasticity of the carotid artery, the recovery of blood pressure circadian rhythm, and the therapeutic effect of antihypertension in EH patients between the two groups (P>0.05). CONCLUSIONS: Chinese herbal medicine for CGSHY may lower the blood pressure smoothly and recover the circadian rhythm of blood pressure in EH patients. They may also improve the carotid elasticity of EH patients similar to that of Enalapril. The mechanism of action of Chinese herbs on EH might be related to the regulation of vascular endothelium function.


Assuntos
Artérias/fisiopatologia , Pressão Sanguínea/fisiologia , Ritmo Circadiano/fisiologia , Medicamentos de Ervas Chinesas/uso terapêutico , Elasticidade/fisiologia , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Anti-Hipertensivos , Artérias/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Monitorização Ambulatorial da Pressão Arterial , Ritmo Circadiano/efeitos dos fármacos , Elasticidade/efeitos dos fármacos , Enalapril/farmacologia , Enalapril/uso terapêutico , Endotelina-1/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Fatores de Tempo , Resultado do Tratamento , Yin-Yang
7.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 33(8): 755-60, 2008 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-18772520

RESUMO

OBJECTIVE: To explore the value of transthoracic echocardiography (TTE) in transcatheter closure of atrial septal aneurysm (ASA) combined with secoundum-type atrial septal defect (ASD). METHODS: Fourteen patients (3 males and 11 females) who had ASA combined with secoundum-type ASD were diagnosed by TTE or transesophageal echocardiography. The ASA projected to the right atrium in all patients. The width of basilar part was 13 approximately 24 (18.5+/-3.9) mm, and the vertical extent was 7 approximately 11(9.7+/-1.8) mm. Ten patients combined with single hole ASD and 4 patients with multiple hole ASD. Blood shifting from the left atrium to the right atrium was displayed in color Doppler in all patients. All patients were treated by transcatheter closure under the guiding of X fluoroscopy and TTE, and examined with TTE during the follow-up. RESULTS: Transcatheter closure was successfully performed by 14 occluders in all patients. No residual shunt was detected immediately by TTE after the procedure in all patients. During the 6 approximately 12 month follow-up, no residual shunt or occluder shifting was found, the dimensions of the heart became normal in 11 patients (79%) and were significantly decreased in 4. CONCLUSION: Transcatheter closure is feasible in patients with ASA combined with secoundum-type ASD, and extra attention must be paid to the specialty. TTE is very important in case selection before transcatheter closure, and it may be used to monitor and guide the procedure during transcatheter closure.


Assuntos
Oclusão com Balão/métodos , Cateterismo Cardíaco , Aneurisma Cardíaco/terapia , Comunicação Interatrial/terapia , Adulto , Septo Interatrial , Ecocardiografia , Feminino , Aneurisma Cardíaco/complicações , Comunicação Interatrial/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Ultrassonografia de Intervenção , Adulto Jovem
8.
Br J Clin Pharmacol ; 64(3): 346-52, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17439540

RESUMO

AIMS: Pravastatin is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, which is widely used both in primary and secondary prevention of coronary heart disease (CHD). Pravastatin is not subject to metabolism by cytochrome P450s, but it is actively transported from blood into target tissues (e.g. hepatocytes in the liver) by the organic anion transporting polypeptide 1B1 (OATP1B1), encoded by SLCO1B1. The aim of the present study was to evaluate the impact of SLCO1B1 521T-->C (Val174Ala) functional genetic polymorphism on the lipid-lowering efficacy of multiple-dose pravastatin in Chinese patients with CHD. METHODS: Forty-five hospitalized patients with CHD prospectively received pravastatin as a single-agent therapy (20 mg day(-1) p.o.) for 30 days. Serum triglycerides, total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol concentrations were determined before and after pravastatin treatment. RESULTS: Pravastatin treatment significantly decreased plasma lipids in all patients (P < 0.001). Importantly, we showed an attenuated pravastatin pharmacodynamic effect on total cholesterol in patients with 521TC heterozygote genotype (from 5.52 +/- 0.51 mmol l(-1) to 4.70 +/- 0.35 mmol l(-1), % change -14.5 +/- 6.6%, N = 9) compared with 521TT homozygote genotype (from 5.47 +/- 1.15 mmol l(-1) to 4.21 +/- 0.89 mmol l(-1), % change -22.4 +/- 10.3%, N = 36) (mean +/- SD, P = 0.03, two-tailed test with alpha set at 5%). SLCO1B1 521T-->C functional polymorphism did not significantly influence pravastatin pharmacodynamics on other plasma lipids (P > 0.05). CONCLUSIONS: The 521T-->C polymorphism of SLCO1B1 appears to modulate significantly the total cholesterol-lowering efficacy of pravastatin in Chinese patients with CHD. Further studies are warranted to determine the extent to which SLCO1B1 genetic variation may contribute to resistance to pravastatin in Asian patients treated with standard doses of pravastatin.


Assuntos
Anticolesterolemiantes/farmacologia , Doença das Coronárias/tratamento farmacológico , Lipídeos/sangue , Transportadores de Ânions Orgânicos/genética , Polimorfismo Genético , Pravastatina/farmacologia , Adulto , Idoso , Anticolesterolemiantes/uso terapêutico , Povo Asiático , Colesterol/metabolismo , Feminino , Genótipo , Humanos , Transportador 1 de Ânion Orgânico Específico do Fígado , Masculino , Pessoa de Meia-Idade , Pravastatina/genética , Pravastatina/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento
9.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 31(5): 629-34, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17062919

RESUMO

OBJECTIVE: investigate and compare the effect of valsartan and indapamide on inflammatory cytokines in hypertension. METHODS: Forty-one untreated patients with mild to moderate hypertension and 20 age and sex-matched normotensives were enrolled in this study. Hypertensives were treated with indapamide 1.5 mg/d (n=20) or valsartan 80 mg/d (n=21) for 4 weeks, and blood samples for determining monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1 (MIP-1alpha), sP-selectin, asymmetric dimethylarginin (ADMA), angiotensin II (Ang II), and 6-keto-PGF1alpha were collected before the treatment and 4 weeks after the treatment. RESULTS: Hypertensives exhibited significantly higher blood pressure, as well as elevated plasma levels of MCP-1, MIP-1alpha, sP-selectin and serum level of ADMA compared with the normotensives. Nevertheless, there was no significant difference in serum 6-keto-PGF1alpha and Ang II between the hypertensives and the normotensives. After the treatment with indapamide or valsartan for 4 weeks, both the systolic and diastolic blood pressures, though still higher than those of the normotensives, decreased markedly. After the treatment with indapamide for 4 weeks, MCP-1, MIP-1alpha and sP-selectin slightly decreased, but not statistically significant (P>0.05). Those cytokines decreased significantly after being treated with valsartan for 4 weeks [(19.16+/-3.11) pg/mL vs (16.08+/-2.67) pg/mL, P<0.05; (27.74+/-8.36) pg/mL vs (17.64+/-7.59) pg/mL, P<0.05; (2.67+/-3.18) pg/mL vs (6.15+/-2.94) pg/mL, P<0.01]. In the 2 treatment groups, 6-keto-PGF1alpha markedly increased [(61.96+/-20.81) pg/mL vs (96.72+/-25.89) pg/mL, P<0.05; (63.25+/-16.92) pg/mL vs (143.22+/-43.45) pg/mL, P<0.01]; ADMA decreased significantly [(1.35+/-0.74) pg/mL vs (0.98+/-0.56) micromol/L, P<0.05; (1.31+/-0.68) pg/mL vs (0.71+/-0.52) micromol/L, P<0.01]. Though Ang II slightly increased, no statistical significance was found (P>0.05). CONCLUSION: The levels of MCP-1, MIP-1alpha, sP-selectin and ADMA were elevated in mild to moderate hypertensives. Valsartan and indapamide have similar blood pressure lowering effect. Valasartan exerts more significant effect on cytokines than indapamide does.


Assuntos
Anti-Hipertensivos/uso terapêutico , Citocinas/sangue , Hipertensão/tratamento farmacológico , Indapamida/uso terapêutico , Tetrazóis/uso terapêutico , Valina/análogos & derivados , Adulto , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Quimiocina CCL2/sangue , Quimiocina CCL3 , Quimiocina CCL4 , Diuréticos/uso terapêutico , Feminino , Humanos , Hipertensão/sangue , Proteínas Inflamatórias de Macrófagos/sangue , Masculino , Pessoa de Meia-Idade , Selectina-P/sangue , Valina/uso terapêutico , Valsartana
10.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 31(1): 66-9, 2006 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-16562679

RESUMO

OBJECTIVE: To investigate the protective effect of losartan against on injury induced by ox-LDL in endothelial cells and the relationship with asymmetric dimethylarginine (ADMA). METHODS: Endothelial injury was induced by incubation with ox-LDL 100 mg/L in cultured HUVECs for 24 h, and the levels of ADMA, lactate dehydrogenase (LDH), nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) in the conditioned medium were measured. The activity of dimethylarginine dimethylaminohydrolase (DDAH) of cultured endothelial cells was also determined. RESULTS: Incubation of endothelial cells with ox-LDL 100 mg/L for 24 h induced a marked elevation of the levels of ADMA, LDH and TNF-alpha in the conditioned medium and a significant decrease in the activity of DDAH and the content of NO (P < 0.05). Pretreatment with losartan (10(-8) - 10(-6) mmol/L) significantly inhibited the increased levels of ADMA, LDH and TNF-alpha, attenuated the decreased levels of NO and the decreased activity of DDAH induced by ox-LDL (P < 0.05). CONCLUSION: Losartan may preserve ox-LDL-induced endothelial cell injury by increasing the DDAH activity and decreasing the ADMA level.


Assuntos
Arginina/análogos & derivados , Endotélio Vascular/patologia , Lipoproteínas LDL/efeitos adversos , Losartan/farmacologia , Amidoidrolases/metabolismo , Arginina/análise , Células Cultivadas , Humanos , L-Lactato Desidrogenase/análise , Óxido Nítrico/análise , Substâncias Protetoras/farmacologia , Veias Umbilicais/citologia
11.
Int J Cardiol ; 110(1): 60-6, 2006 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-16242797

RESUMO

BACKGROUND: Previous study has demonstrated an arterial inflammatory response in aortic tissues in several hypertensive models which can not be fully explained by hemodynamic forces. This study sought to investigate the effect of angiotensin II (Ang II)and its subtype-1 receptor blocker Losartan on the chemokine expression of monocyte chemoattractant protein-1(MCP-1) in aortic tissues of acute stage of 2-kidney-1-clip (2K1C) hypertensive rats. METHODS: 2K1C renovascular hypertension was produced in male Wistar-Kyoto(WKY) rats by placing a silver clip with an internal diameter of 0.2 mm around the left renal artery. The MCP-1 mRNA on aortic wall was detected by in situ hybridization and reverse transcription-polymerase chain reaction(RT-PCR); the levels of Ang II in plasma and aorta were determined by radioimmunoassay. The concentration of MCP-1 in supernatant of cultured endothelial cells (ECV-304) was measured by ELISA. RESULTS: No MCP-1 was exhibited in aortic wall of normotensive rats both by RT-PCR and in situ hybridization; it would be expressed on the aortic wall of rats in 7 days after 2K1C hypertensive model was formed, especially in intima. The expression of MCP-1 in aortic wall was increased with the duration of hypertension and correlated with local Ang II activity (r=0.594, P=0.02) other than those in plasma, it was decreased obviously after being treated by Losartan for 28 days (optical density of MCP-1/GAPDH ratio: 0, 0.58+/-0.10, 1.14+/-0.09, 1.52+/-0.20, 0.66+/-0.07, respectively, P<0.01). Ang II had increased the expression of MCP-1 in endothelial cells; the highest levels had been performed at 1x10(-7)mol/l Ang II or after 4 h, respectively; and losartan markedly reduced the expression of MCP-1. CONCLUSIONS: The expression of MCP-1 significantly increases in aortic tissues of the acute stage 2K1C hypertensive rats and is decreased markedly by treatment of losartan. These findings imply Ang II may be involved in facilitating MCP-1 production in hypertension, and may provide a molecular link between hypertension and the development of atherosclerosis.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Anti-Hipertensivos/farmacologia , Aorta/efeitos dos fármacos , Quimiocina CCL2/metabolismo , Hipertensão Renovascular/metabolismo , Losartan/farmacologia , Angiotensina II/metabolismo , Animais , Aorta/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Quimiocina CCL2/genética , Ensaio de Imunoadsorção Enzimática , Hipertensão Renovascular/tratamento farmacológico , Hibridização In Situ , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Radioimunoensaio , Ratos , Ratos Endogâmicos WKY , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima
13.
Naunyn Schmiedebergs Arch Pharmacol ; 371(5): 401-7, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15915325

RESUMO

Previous investigations have demonstrated that endogenous inhibitors of nitric oxide synthase (NOS), such as asymmetric dimethylarginine (ADMA), contribute importantly to endothelial dysfunction, and that fenofibrate has a protective effect on the endothelium in rats treated with low-density lipoprotein (LDL) by reducing ADMA levels. In the present study, we explored further the possible mechanism underlying inhibition of ADMA generation by fenofibrate in cultured human umbilical vein endothelial cells (HUVECs). Endothelial injury was induced in cultured HUVECs by incubation with oxidative LDL (ox-LDL) and the levels of ADMA, lactate dehydrogenase (LDH), NO and tumour necrosis factor-alpha (TNF-alpha) in the conditioned medium were measured. Cell viability and the activity of dimethylarginine dimethylaminohydrolase (DDAH) and nuclear factor-kappaB (NF-kappaB) in the cultured HUVECs were also determined. Incubation of HUVECs with ox-LDL (100 microg/ml) for 24 h markedly elevated ADMA, LDH and TNF-alpha in the conditioned medium and significantly increased the activity of NF-kappaB, concomitantly with a significant decrease in the activity of DDAH and the content of NO. Pretreatment with fenofibrate (3, 10 or 30 microM) significantly inhibited the increases in ADMA, LDH and TNF-alpha, attenuated the decreased levels of NO and the decreased activity of DDAH and prevented the activation of NF-kappaB. Similar effects were observed in the presence of pyrrolidine dithiocarbamate (PDTC, 10 microM), an antagonist of NF-kappaB. The beneficial effects of fenofibrate on cultured endothelial cells were abolished by MK-886, a specific peroxisome proliferator-activated receptor-alpha (PPARalpha) antagonist. The present results suggest that fenofibrate inhibits ox-LDL-induced endothelial cell damage by decreasing ADMA and increasing DDAH activity, and the protective effects of fenofibrate on endothelial cells may be related to reduction of NF-kappaB activity by activation of the PPARalpha receptor.


Assuntos
Arginina/análogos & derivados , Fenofibrato/farmacologia , Hipolipemiantes/farmacologia , NF-kappa B/antagonistas & inibidores , Arginina/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Humanos , L-Lactato Desidrogenase/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Óxido Nítrico/metabolismo , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
14.
Int J Cardiol ; 100(3): 495-8, 2005 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-15837096

RESUMO

Previous studies have shown that endothelin-1 (ET-1) may play a pathophysiological role in myocardial ischemia/reperfusion injury. In the present study, BMS-182874 significantly improved the recovery of cardiac function and reduced the release of CK during reperfusion after ischemia and the content of tumor necrosis factor (TNF-alpha) in myocardial tissues. BMS-182874 also reduced myocardial injury and the increased level of TNF-alpha by exogenous ET-1. These results suggest that the cardioprotective effects of the ET receptor antagonist may be related to inhibition of TNF-alpha production.


Assuntos
Anti-Hipertensivos/farmacologia , Compostos de Dansil/farmacologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Endotelina-1/fisiologia , Técnicas In Vitro , Masculino , Ratos , Ratos Sprague-Dawley
15.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 29(6): 693-6, 2004 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-16114560

RESUMO

OBJECTIVE: To clarify the formation and function of coronary collateral circulation (CCC) in coronary artery disease (CAD) patients with severe coronary artery stenosis and their influencing factors. METHODS: Coronary angiography was performed on 266 CAD patients with severe coronary stenosis. CCC formation was evaluated by Rentrop rating on those 266 patients and 401 severe stenosis arteries; while in CCC formed patients, CCC function was evaluated by Werner collateral collection (CC) rating. The formation, function of CCC and their influencing factors were analyzed and compared. RESULTS: CCC formation in those severe stenosis coronary arteries was related to the severity of coronary stenosis: the forming rate of CCC was 42.6% in vessels with 90%-94% stenosis (Group A), 56.9% with 95%-99% stenosis (Group B) and 93.0% with 100% stenosis (Group C) (p <0 .01). Between CCC forming and non-forming groups, there was no significant difference in age, gender, incidence of MI, hypertension and diabetes, history of smoking and serum levels of HDL-C and LDL-C (P > 0.05). In the CCC formation group, serum HDL-C level was the highest in the CC Grade 2 group (according to Werner function rating) and the lowest in the CC Grade 0 group (P < 0.05). Whereas, LDL-C level was the lowest in the CC Grade 2 group and the highest in the CC Grade 0 group (P < 0.05). CONCLUSION: Severity of coronary stenosis was the major influencing factor in CCC formation and function, and the rate of CCC formation increased with the exacerbation of coronary stenosis. Serum HDL-C and LDL-C level had no relationship with CCC formation, but related to CCC function. Better CCC function was found in patients with high level of HDL-C whereas the patients with high level of LDL-C had spoiled CCC function.


Assuntos
Circulação Colateral/fisiologia , Angiografia Coronária , Doença da Artéria Coronariana/fisiopatologia , Circulação Coronária , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Circulação Coronária/fisiologia , Feminino , Humanos , Masculino
16.
Hunan Yi Ke Da Xue Xue Bao ; 28(2): 145-8, 2003 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-12934361

RESUMO

OBJECTIVE: To investigate the expression of monocyte chemoattractant protein-1(MCP-1) of aorta wall in acute phase of hypertension in rats with 2 kidney and 1 clip(2K1C). METHOD: The MCP-1 mRNA on aorta wall was detected by in situ hybridization and reverse transcription-polymerase chain reaction(RT-PCR). RESULTS: No MCP-1 was expressed in normal rat, but it was expressed on the aorta wall of rats in 1 week after 2K1C hypertensive model was formed. The expression of MCP-1 increased with the development of hypertension. CONCLUSION: The expression of MCP-1 on aorta wall of 2K1C hypertensive rats increases in the early stage of hypertension, which may play an important role in accelerating atherosclerosis.


Assuntos
Aorta/metabolismo , Quimiocina CCL2/biossíntese , Hipertensão/metabolismo , Animais , Arteriosclerose/etiologia , Quimiocina CCL2/genética , Hipertensão/complicações , Masculino , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Wistar
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