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Exp Ther Med ; 16(5): 3875-3882, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30344664


Effects of toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway on expression of angiotensinogen and AT1a receptor were investigated, to explore the role of TLR4/NF-κB signaling pathway in cardiovascular disease. Neonatal rat left ventricular myocytes (NRVMs) were cultured and cardiomyocytes were identified by immunocytochemical staining of sarcomeric α-actin. NRVMs were treated with lipopolysaccharide (LPS) at a dose of 10, 100 and 1,000 ng/ml, and RT-PCR was performed 24 h later to detect the expression of TLR4, angiotensinogen (ATG) and AT1a at mRNA level. NRVMs were cultured and pretreated with caffeic acid phenethylester (CAPE) for 30 min. Then NRVMs were stimulated with LPS (1,000 ng/ml) for 24 h. Nuclear translocation of NF-κB p65 was detected by immunocytochemistry. Expression of TLR4, angiotensinogen and AT1a receptor after CAPE stimulation was detected by RT-PCR. TLR4 mRNA was highly expressed in in vitro cultured NRVMs, and the expression level was significantly increased by LPS (10-1,000 ng/ml) stimulation in a dose-dependent manner (P<0.05). LPS stimulation also significantly increased the expression levels of angiotensinogen and AT1a receptor in a dose-dependent manner (P<0.05). NF-κB was activated and nuclear translocation of NF-κB p65 occurred after stimulation with LPS (1,000 ng/ml) for 24 h, while CAPE (20 µg/ml) inhibited the nuclear translocation of NF-κB p65 and inhibited LPS-induced expression of angiotensinogen and AT1a receptor. With LPS stimulation, TLR4 signaling positively regulates the expression of TLR4 and upregulates the expression of angiotensinogen and AT1a receptor in NRVMs. CAPE, an inhibitor of NF-κB, inhibited NF-κB p65 activation and inhibited the upregulation of TLR4, angiotensinogen and AT1a receptors induced by LPS. These results suggest that NF-κB plays a key regulatory role in the above-mentioned effects induced by LPS. Intervention with TLR4/NF-κB signaling may become a new target for prevention and treatment of cardiovascular diseases.

Exp Ther Med ; 14(4): 3569-3572, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29042949


Granulomatosis with polyangiitis (GPA) often causes small blood vessel lesions in multiple organs, with less impact on large vessels. We report a case involving not only large blood vessels, but also angina. The computed tomographic angiography of large vessels and vascular ultrasonography of the extremity also suggested great arteries of the body were involved. Further cytoplasmic antineutrophil cytoplasmic antibody tests, pathological examination and dynamic chest computed tomography scan confirmed the diagnosis of GPA. Anti-inflammatory therapy and coronary secondary prevention were given after diagnosis by pathological examination and laboratory evaluation. The symptoms of angina pectoris were relieved. This rare case report reminds us that among the well-known risk factors of atherosclerotic diseases, GPA is also an important risk factor for acute coronary syndrome. Early foresight for this rare risk factor can improve the early diagnosis and treatment of the disease, which will improve the prognosis of the patients.

Heart Vessels ; 31(8): 1218-29, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26290166


We decided to assess the prognostic value of NLRP3 inflammasome level in acute coronary syndrome (ACS) patients and whether it was related to coronary atherosclerotic severity. Study population included one-hundred and twenty-three (123) subjects. Peripheral blood monocyte NLRP3 protein level was correlated with clinical presentation, angiographic characteristics and its scoring systems as well as GRACE and TIMI risk scores. Follow-up for major adverse cardiac events (MACE) was carried out at 180 days. Peripheral blood monocyte NLRP3 was found to be elevated in ACS patients (P < 0.05) and showed positive correlation with GRACE score (r = 0.619), TIMI score (r = 0.580), SYNTAX score (r = 0.550), Clinical SYNTAX score (r = 0.564) and Gensini score (r = 0.516). NLRP3 was also increased with increasing number of vessels, the number of lesions present and the presence bifurcation lesions (P < 0.05). Multivariate Cox regression analysis showed NLRP3 to be an independent predictor of MACE (P = 0.043). Kaplan-Meier analysis and receiver operating characteristic curves for NLRP3 showed good predictive value for MACE. There is a positive correlation of NLRP3 level with severity of coronary atherosclerosis. NLRP3 level is a promising prognostic utility and is efficient in event prediction for MACE.

Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/mortalidade , Doença da Artéria Coronariana/sangue , Creatinina/sangue , Lipídeos/sangue , Proteína 3 que Contém Domínio de Pirina da Família NLR/sangue , Idoso , Estudos de Casos e Controles , Angiografia Coronária , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença
Coron Artery Dis ; 26(5): 409-21, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25946654


OBJECTIVES: Despite recent advances in the understanding of the role of NLRP3 inflammasomes in coronary atherosclerosis, further work on their activation and clinical implications remains to be performed. In this study, we aimed to evaluate the effect of the dose of rosuvastatin on NLRP3 and cathepsin-B expression in peripheral blood monocytes in patients with acute coronary syndrome. METHODS: A total of 123 participants were enrolled in this study; these included acute myocardial infarction (AMI) patients (n=53), unstable angina patients (UA, n=40), and normal controls (n=30). AMI and UA patients were divided into high-dose rosuvastatin (20 mg) and low-dose rosuvastatin (5 mg) groups. NLRP3, cathepsin-B, and downstream cytokine expressions were appropriately evaluated using real-time PCR, flow cytometry, western blotting and enzyme-linked immunosorbent assay. The concentrations of serum inflammatory markers were also evaluated for correlation with NLRP3 levels. RESULTS: AMI and UA patients had higher NLRP3, cathepsin-B, interleukin-18 (IL-18), pro-IL-18, IL-1ß, and pro-IL-1ß expressions as compared with the control group (P<0.05). This corresponded with higher levels of serum total cholesterol, serum low-density lipoprotein cholesterol, and oxidized low-density lipoprotein in UA and AMI patients (P<0.05). Rosuvastatin at a concentration of 20 mg led to a significant decrease (P<0.05) in the expressions of NLRP3, cathepsin-B, and their downstream cytokines as compared with 5 mg rosuvastatin (P>0.05) from baseline to 4 weeks. This study also showed a positive correlation between NLRP3, cathepsin-B, and downstream inflammatory mediators. CONCLUSION: NLRP3 is involved in inflammation that leads to atherosclerosis. A high dose of rosuvastatin can modulate the inflammatory process of atherosclerosis by downregulating the expression of NLRP3, cathepsin-B, and their downstream mediators. These findings provide insight into the pathogenesis and management of acute coronary syndrome, with NLRP3 as the potential target.

Síndrome Coronariana Aguda/tratamento farmacológico , Angina Instável/tratamento farmacológico , Anti-Inflamatórios/administração & dosagem , Proteínas de Transporte/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inflamassomos/sangue , Mediadores da Inflamação/sangue , Monócitos/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Rosuvastatina Cálcica/administração & dosagem , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/genética , Síndrome Coronariana Aguda/imunologia , Adulto , Idoso , Angina Instável/sangue , Angina Instável/diagnóstico , Angina Instável/genética , Angina Instável/imunologia , Biomarcadores/sangue , Proteínas de Transporte/genética , Proteínas de Transporte/imunologia , Catepsina B/sangue , China , Citocinas/sangue , Feminino , Humanos , Inflamassomos/genética , Inflamassomos/imunologia , Mediadores da Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/metabolismo , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/genética , Infarto do Miocárdio/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Fatores de Tempo , Adulto Jovem