RESUMO
Fibroblast growth factor 21 (FGF-21) is an endocrine factor that can be secreted into circulation by the liver. FGF-21 takes part in metabolic actions and is thought to be a promising candidate for the treatment of diabetes. However, the role of FGF-21 in atherosclerosis is unknown. In this study, apoE(-/-) mice were fed an atherogenic diet for 4 weeks with and without subcutaneous injections of FGF-21. ApoE(-/-) mice fed an atherogenic diet showed hyperlipidemia, a large plaque area in aortas and increased vessel wall thickness. Plasma FGF-21 content and protein level of FGF receptor 1 (FGFR1) in aortas was greater in apoE(-/-) than C57BL/6J mice. Exogenous FGF-21 treatment significantly ameliorated dyslipidemia in apoE(-/-) mice. FGF-21-treated apoE(-/-) mice showed reduced number of aortic plaques and plaque area as well as reduced number of TUNEL-positive cells. Protein levels of the endoplasmic reticulum stress markers glucose-regulated protein 94, caspase-12 and C/EBP homologous protein were reduced by 34.5, 31.4 and 26.5 %, respectively, in apoE(-/-) mice. Endogenous expression of FGF-21 and its receptor FGFR1 were upregulated in apoE(-/-) mice, and exogenous administration of FGF-21 ameliorated the atherogenic-induced dyslipidemia and vascular atherosclerotic lesions. FGF-21 protecting against atherosclerosis might be in part by its inhibitory effects on endoplasmic reticulum stress-mediated apoptosis.
Assuntos
Apolipoproteínas E/deficiência , Apoptose , Aterosclerose/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fatores de Crescimento de Fibroblastos/biossíntese , Animais , Apolipoproteínas E/sangue , Aterosclerose/etiologia , Aterosclerose/patologia , Western Blotting , Modelos Animais de Doenças , Dislipidemias/complicações , Dislipidemias/metabolismo , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/uso terapêutico , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RadioimunoensaioRESUMO
OBJECTIVE: To determine whether early catheterization laboratory activation would reduce median door-to-balloon time in patients with ST elevation myocardial infarction (STEMI). METHODS: Consecutive patients with STEMI underwent primary percutaneous coronary intervention (PCI) from January 2006 to December 2008 in Beijing Anzhen Hospital were analyzed. Patients were divided into three groups. Group A included patients without prehospital ECG (n = 168), group B included patients with prehospital ECG (n = 224) and group C included patients with prehospital ECG and early telephonic notification to activate catheterization laboratory (n = 114). Primary end point was door-to-balloon time, secondary end points included peak Troponin I elevation, left ventricular ejection fraction, length of hospital stay, hospital mortality and 30 days follow-up mortality. RESULTS: Baseline characteristics were similar among groups. Door-to-balloon time and door-to-catheter laboratory time (110 minutes, 94 minutes and 85 minutes, respectively, all P < 0.01; 91 minutes, 74 minutes and 64 minutes, respectively, all P < 0.01) were significantly shorter in group B and C than those in group A. The percentage of patients with door-to-balloon time less than 90 minutes increased significantly from 32% in group A to 43% in group B and 59% in group C (P < 0.01). CONCLUSION: Early activation of catheterization laboratory by prehospital ECG and telephonic notification could markedly reduce door-to-balloon time in patients with STEMI.
Assuntos
Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Idoso , Angioplastia Coronária com Balão , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
OBJECTIVE: To analyze the clinical characteristics and angiographic features of myocardial infarction in women aged 40 or less. METHODS: The clinical information and angiographic images of 13 young female patients with myocardial infarction treated in Beijing Anzhen Hospital during the past 6 years were collected and analyzed. RESULTS: The traditional risk factors especially hypertension and dyslipidaemia were more frequent in young female patients with myocardial infarction. Women were more likely to experience angina as their first symptom. Most of the patients did not seek medical service in early time. An infarct related artery and an obviously complex coronary lesion were found in all (100%) the cases (left anterior descending 50%). Two vessel diseases were prevalent in these patients. CONCLUSIONS: Young female patients with myocardial infarction are characterized by a higher rate of modifiable risk factors. They often have severe coronary lesion and multivessel disease.
Assuntos
Angiografia Coronária , Infarto do Miocárdio , Angina Pectoris , Doença da Artéria Coronariana , Feminino , Humanos , Fatores de RiscoRESUMO
OBJECTIVES: Chronic total occlusion (CTO) is prevalent in patients with prior coronary artery bypass grafting (CABG). However, data available concerning the prevalence of new-onset CTO of native vessels in patients with prior CABG is limited. Therefore, the objective of the study is to determine predictors for new native-vessel occlusion in patients with prior coronary bypass surgery. METHODS: 354 patients with prior CABG receiving follow-up angiography are selected and analyzed in the present study, with clinical and angiographic variables being analyzed by logistic regression to determine the predictors of new native-vessel occlusion. RESULTS: The overall new occlusion rate was 35.59%, with multiple CTOs (42.06%) being the most prevalent (LAD 24.60% and RCA 18.25%, respectively). Additionally, current smoking (OR: 2.67; 95% CI: 2.60 to 2.74; p=0.01), reduced ejection fraction (OR: 1.76; 95% CI: 1.04 to 2.97; p=0.04), severe stenosis (OR: 3.65; 95% CI: 2.55 to 5.24; p=0.01), and diabetes mellitus (OR: 1.86; 95% CI: 1.34 to 2.97; p=0.04) serve as the independent predictors for new native-vessel occlusion. CONCLUSION: As to high incidence of postoperative CTO, appropriate revascularization strategies and postoperative management should be taken into careful consideration.
RESUMO
BACKGROUND: Chronic kidney disease (CKD) is closely related to the cardiovascular events in vascular calcification (VC). However, little has known about the characteristics of kidney injury caused by VC. Fibroblast growth factor 21 (FGF21) is an endocrine factor, which takes part in various metabolic actions with the potential to alleviate metabolic disorder diseases. Even FGF21 has been regarded as a biomarker in CKD, the role of FGF21 in CKD remains unclear. Therefore, in this study, we evaluate the FGF21 on the kidney injury in VC rats. METHODS: The male Sprague-Dawley rats were divided into three groups: (1) control group, (2) Vitamin D3 plus nicotine (VDN)-induced VC group, (3) FGF21-treated VDN group. After 4 weeks, the rats were killed and the blood was collected for serum creatinine, urea nitrogen, calcium, and phosphate measurement. Moreover, the renal tissues were homogenized for alkaline phosphatases (ALPs) activity and calcium content. The levels of FGF21 protein were measured by radioimmunoassay. The levels of ß-Klotho and FGF receptor 1 (FGFR1) protein were measured by enzyme-linked immunosorbent assay (ELISA). The structural damage and calcifications in aortas were stained by Alizarin-red S. Moreover, the structure of kidney was observed by hematoxylin and eosin staining. RESULTS: The renal function impairment caused by VDN modeling was ameliorated by FGF21 treatment, inhibited the elevated serum creatinine and urea level by 20.5% (34.750 ± 4.334 µmol/L vs. 27.630 ± 2.387 µmol/L) and 4.0% (7.038 ± 0.590 mmol/L vs. 6.763 ± 0.374 mmol/L; P < 0.01), respectively, together with the structural damages of glomerular atrophy and renal interstitial fibrosis. FGF21 treatment downregulated the ALP activity, calcium content in the kidney of VC rats by 42.1% (P < 0.01) and 11.7% (P < 0.05) as well as ameliorated the aortic injury and calcification as compared with VDN treatment alone group, indicating an ameliorative effect on VC. ELISA assays showed that the expression of ß-Klotho, a component of FGF21 receptor system, was increased in VDN-treated VC rats by 37.4% (6.588 ± 0.957 pg/mg vs. 9.054 ± 0.963 pg/mg; P < 0.01), indicating an FGF21-resistant state. Moreover, FGF21 treatment downregulated the level of ß-Klotho in renal tissue by 16.7% (9.054 ± 0.963 pg/mg vs. 7.544 ± 1.362 pg/mg; P < 0.05). However, the level of FGFR1, the receptor of FGF21, kept unchanged under VDN and VDN plus FGF21 administration (0.191 ± 0.0376 ng/mg vs. 0.189 ± 0.032 ng/mg vs. 0.181 ± 0.034 ng/mg; P > 0.05). CONCLUSIONS: In the present study, FGF21 was observed to ameliorate the kidney injury in VDN-induced VC rats. FGF21 might be a potential therapeutic factor in CKD by cutting off the vicious circle between VC and kidney injury.
Assuntos
Fatores de Crescimento de Fibroblastos/uso terapêutico , Nefropatias/tratamento farmacológico , Insuficiência Renal/tratamento farmacológico , Calcificação Vascular/tratamento farmacológico , Animais , Cálcio/metabolismo , Fatores de Crescimento de Fibroblastos/farmacologia , Masculino , Proteínas de Membrana/metabolismo , Fosfodiesterase I/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: The disruption of physiologic vascular smooth muscle cell (VSMC) migration initiates atherosclerosis development. The biochemical mechanisms leading to dysfunctional VSMC motility remain unknown. Recently, cytokine BMP-2 has been implicated in various vascular physiologic and pathologic processes. However, whether BMP-2 has any effect upon VSMC motility, or by what manner, has never been investigated. METHODS: VSMCs were adenovirally transfected to genetically overexpress BMP-2. VSMC motility was detected by modified Boyden chamber assay, confocal time-lapse video assay, and a colony wounding assay. Gene chip array and RT-PCR were employed to identify genes potentially regulated by BMP-2. Western blot and real-time PCR detected the expression of myosin Va and the phosphorylation of extracellular signal-regulated kinases 1/2 (Erk1/2). Immunofluorescence analysis revealed myosin Va expression locale. Intracellular Ca(2+) oscillations were recorded. RESULTS: VSMC migration was augmented in VSMCs overexpressing BMP-2 in a dose-dependent manner. siRNA-mediated knockdown of myosin Va inhibited VSMC motility. Both myosin Va mRNA and protein expression significantly increased after BMP-2 administration and were inhibited by Erk1/2 inhibitor U0126. BMP-2 induced Ca(2+) oscillations, generated largely by a "cytosolic oscillator". CONCLUSION: BMP-2 significantly increased VSMCs migration and myosin Va expression, via the Erk signaling pathway and intracellular Ca(2+) oscillations. We provide additional insight into the pathophysiology of atherosclerosis, and inhibition of BMP-2-induced myosin Va expression may represent a potential therapeutic strategy.
Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Músculo Liso Vascular/citologia , Cadeias Pesadas de Miosina/metabolismo , Miosina Tipo V/metabolismo , Animais , Proteína Morfogenética Óssea 2/genética , Cálcio/metabolismo , Movimento Celular , Células Cultivadas , Microscopia de Vídeo , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Cadeias Pesadas de Miosina/antagonistas & inibidores , Cadeias Pesadas de Miosina/genética , Miosina Tipo V/antagonistas & inibidores , Miosina Tipo V/genética , Fosforilação , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Transdução de Sinais , Regulação para CimaRESUMO
BACKGROUND: Acute kidney injury (AKI) is associated with poor prognosis after cardiopulmonary bypass. The aim of this retrospective study was to investigate whether stent implantation before cardiopulmonary bypass has beneficial effect on development of AKI in renal artery stenosis (RAS) patients. METHODS: In this retrospective study, patients with abnormal baseline serum creatinine (SCr, > 106 µmol/L) were not included. Included patients (n = 69) were divided into two groups. Group 1 included 31 RAS patients receiving no stent implantation before cardiopulmonary bypass. Group 2 included 38 RAS patients having received stent implantation just before cardiopulmonary bypass. To assess AKI after cardiopulmonary bypass, serum urea nitrogen, SCr and creatinine clearance were recorded at baseline, at the end of operation, during the first and second postoperative 24 hours. RESULTS: Baseline characteristics were similar between groups. Serum urea nitrogen, SCr, creatinine clearance before and after cardiopulmonary bypass were also similar class groups. Incidence of AKI in group 1 was not significantly different from group 2. In group 1, AKI defined by RIFLE between occurred in 7 (22.6%) patients: 5 (16.1%) with RIFLE-R, 2 (6.5%) with RIFLE-I, and no patients with RIFLE-F. In group 2, 10 patients (26.3%) had an episode of AKI during hospitalization: 6 (15.8%) had RIFLE-R, 4 (10.5%) had RIFLE-I, and no patients had RIFLE-F. CONCLUSIONS: There are no data suggesting that it is necessary to stent RAS patients with normal SCr before cardio-pulmonary bypass. However, it cannot be concluded that RAS is not associated with AKI after cardiopulmonary bypass.
Assuntos
Ponte Cardiopulmonar/métodos , Obstrução da Artéria Renal/cirurgia , Idoso , Feminino , Hemodinâmica , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the efficacy and safety of ezetimibe on uncontrolled LDL-C when added to ongoing statin therapy in patients with coronary heart diseases (CHD) and diabetes mellitus (DM). METHODS: 61 patients with LDL-C level exceeding target goal (<2.07 mmol/L) after 12 weeks' treatment with statins, received ezetimibe in addition to their ongoing statin therapy for 8 weeks. Lipid parameters, alanine aminotransferase (ALT), aspartic aminotransferase (AST) and creatine kinase (CK) were compared before and after the adding of ezetimibe. RESULTS: LDL-C before and after the adding of ezetimibe was (2.74+/-0.43) mmol/L and (2.19+/-0.32) mmol/L, respectively (P=0.03) in 61 patients. Ezetimibe added to statin therapy significantly reduced the LDL-C level and TC level by additional 20.1% and 19.1%, respectively (P<0.05). 74% (45/61) patients treated with ezetimibe added to statin reached their target LDL-C goal. No change of TG and HDL-C was observed and no change of AST, ALT and CK was found either. CONCLUSION: Ezetimibe added to statin therapy lowered LDL-C level further and improved the goal attainment in patients with CHD and DM.
Assuntos
Anticolesterolemiantes/uso terapêutico , Azetidinas/uso terapêutico , Doença das Coronárias/complicações , Complicações do Diabetes/sangue , Hipercolesterolemia/tratamento farmacológico , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Doença das Coronárias/sangue , Creatina Quinase/sangue , Quimioterapia Combinada , Ezetimiba , Humanos , Resultado do Tratamento , Triglicerídeos/sangueRESUMO
BACKGROUND: Emergency medical service plays a key role in the early recognition and treatment of ST-elevation myocardial infarction (STEMI), but studies indicate that the patients experiencing STEMI symptoms often fail to call an ambulance as recommended. This study aimed to examine the current ambulance transport frequency and ascertain predictors and reasons for not choosing ambulance transportation by the patients with STEMI in Beijing. METHODS: A prospective, cross-sectional survey was conducted from January 1, 2006 through until June 30, 2007 in two tertiary hospitals in Beijing and included consecutive patients with STEMI admitted within 24 hours of onset of symptoms. Data were collected by structured interviews and medical records review. RESULTS: Of the 572 patients, only 172 (30.1%) used an ambulance, and the remaining 400 (69.9%) presented by self-transport. Multivariate analysis showed that age <65 years (OR: 1.220; 95% CI: 1.001-2.043), lower education level (OR: 1.582; 95% CI: 1.003-2.512), presence of pre-infarction angina (OR: 1.595; 95% CI: 1.086-2.347), and attribution of symptoms to non-cardiac origin (OR: 1.519; 95% CI: 1.011-2.284) were independent predictors for not using an ambulance. However, history of coronary artery disease (CAD), dyspnea, perceiving symptoms to be serious, and knowing the meaning of cardiopulmonary resuscitation appeared to be independent predictors of ambulance use. The main reasons for not using an ambulance were convenience and quickness of self-transport and the decreased severity of symptoms. CONCLUSIONS: A large proportion of patients in Beijing do not call for an ambulance after onset of STEMI symptoms. Several factors including demographics, previous CAD, symptoms and cognitive factors of patients are associated with the ambulance use. The public should be educated that an ambulance is not merely a transportation modality and that it also provides rapid diagnosis and treatment.
Assuntos
Ambulâncias/estatística & dados numéricos , Infarto do Miocárdio/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Idoso , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/patologia , Avaliação das Necessidades , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Estudos Prospectivos , Análise de Regressão , Transporte de PacientesRESUMO
OBJECTIVE: To study the change of baseline clinical characteristics including prehospital delayed time (PDT), modes of transportation and treatment for patients with acute myocardial infarction (AMI) in the past 3 years. METHODS: We used the same questionnaire to accurately collect and retrospectively analyze the data regarding clinical characteristics of all 1004 patients with AMI, who consecutively presented to the Emergency Unit and Emergency Intensive Care Unit (EICU) of Beijing Anzhen Hospital from March 12th 2004 to March 11th 2007. According to the time of onset of the disease, all patients were divided into 3 groups: group A (from Mar. 12th 2004 to Mar. 11th 2005), group B (Mar. 12th 2005 to Mar 11th 2006) and group C (Mar. 12th 2006 to Mar. 11th 2007). Clinical characteristics and treatment were compared. RESULTS: There were significant differences in the number of patients with histories of stroke, coronary artery disease or smoking among the three groups (P < 0.05). No obvious differences in the median of PDT were found among the three groups (P > 0.05). More patients accepted reperfusive therapy in group C compared to group A (P < 0.05), although the mortality rates of AMI among these 3 years were similar. CONCLUSION: Though more people started to have accepted reperfusion therapy, mortality failed to show an obvious decrease. Subject as how to shorten the PDT called for further study.
Assuntos
Infarto do Miocárdio/patologia , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Angioplastia Coronária com Balão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/cirurgia , Infarto do Miocárdio/terapia , Reperfusão Miocárdica , Fatores de Tempo , Adulto JovemRESUMO
PROBLEM: This study was carried out to determine the presence of early pregnancy factor (EPF) activity in cervical mucus of pregnant women and explore the relationship between EPF activity in sera suggested it and in cervical mucus. METHOD OF STUDY: Cervical mucus and sera were collected from 60 pregnant women in different terms and 25 non-pregnant women, respectively. EPF activity was detected by rosette inhibition assay. RESULTS: EPF activity did exist in cervical mucus of pregnant women and was similar both in cervical mucus and sera. CONCLUSIONS: We report here for the first time the EPF activity in cervical mucus of pregnant women. The parallel change observed in sera suggested it might be another useful index in evaluating embryo viability.