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1.
PLoS One ; 10(9): e0132415, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26332322

RESUMO

INTRODUCTION: The aim of this study was to determine prognostic factors for the risk of new vascular events during the first 6 months after acute myocardial infarction (AMI) or atherothrombotic stroke (AS). We were interested in the prognostic role of endothelial progenitor cells (EPC) and circulating endothelial cells (CEC). METHODS: Between February 2009 and July 2012, 100 AMI and 50 AS patients were consecutively studied in three Spanish centres. Patients with previously documented coronary artery disease or ischemic strokes were excluded. Samples were collected within 24h of onset of symptoms. EPC and CEC were studied using flow cytometry and categorized by quartiles. Patients were followed for up to 6 months. NVE was defined as new acute coronary syndrome, transient ischemic attack (TIA), stroke, or any hospitalization or death from cardiovascular causes. The variables included in the analysis included: vascular risk factors, carotid intima-media thickness (IMT), atherosclerotic burden and basal EPC and CEC count. Multivariate survival analysis was performed using Cox regression analysis. RESULTS: During follow-up, 19 patients (12.66%) had a new vascular event (5 strokes; 3 TIAs; 4 AMI; 6 hospitalizations; 1 death). Vascular events were associated with age (P = 0.039), carotid IMT≥0.9 (P = 0.044), and EPC count (P = 0.041) in the univariate analysis. Multivariate Cox regression analysis showed an independent association with EPC in the lowest quartile (HR: 10.33, 95%CI (1.22-87.34), P = 0.032] and IMT≥0.9 [HR: 4.12, 95%CI (1.21-13.95), P = 0.023]. CONCLUSIONS: Basal EPC and IMT≥0.9 can predict future vascular events in patients with AMI and AS, but CEC count does not affect cardiovascular risk.


Assuntos
Doenças Cardiovasculares/etiologia , Células Progenitoras Endoteliais/patologia , Infarto do Miocárdio/complicações , Acidente Vascular Cerebral/complicações , Doença Aguda , Idoso , Doenças Cardiovasculares/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Feminino , Seguimentos , Humanos , Hipercolesterolemia/complicações , Hipercolesterolemia/patologia , Hipertensão/complicações , Hipertensão/patologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia , Prognóstico , Fatores de Risco , Acidente Vascular Cerebral/patologia
5.
J Mol Cell Cardiol ; 80: 146-55, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25619946

RESUMO

The mobilization pattern and functionality of endothelial progenitor cells after an acute ischemic event remain largely unknown. The aim of our study was to characterize and compare the short- and long-term mobilization of endothelial progenitor cells and circulating endothelial cells after acute myocardial infarction or atherothrombotic stroke, and to determine the relationship between these cell counts and plasma concentrations of vascular cell adhesion molecule (VCAM-1) and Von Willebrand factor (VWF) as surrogate markers of endothelial damage and inflammation. In addition, we assessed whether endothelial progenitor cells behave like functional endothelial cells. We included 150 patients with acute myocardial infarction or atherothrombotic stroke and 145 controls. Endothelial progenitor cells [CD45-, CD34+, KDR+, CD133+], circulating endothelial cells [CD45-, CD146+, CD31+], VWF, and VCAM-1 levels were measured in controls (baseline only) and in patients within 24h (baseline) and at 7, 30, and 180 days after the event. Myocardial infarction patients had higher counts of endothelial progenitor cells and circulating endothelial cells than the controls (201.0/mL vs. 57.0/mL; p<0.01 and 181.0/mL vs. 62.0/mL; p<0.01). Endothelial progenitor cells peaked at 30 days post-infarction (201.0/mL vs. 369.5/mL; p<0.01), as did VCAM-1 (573.7 ng/mL vs. 701.8 ng/mL; p<0.01). At 180 days post-infarction, circulating endothelial cells and VWF decreased, compared to baseline. In stroke patients, the number of endothelial progenitor cells - but not circulating endothelial cells - was higher than in controls (90.0/mL vs. 37.0/mL; p=0.01; 105.0/mL vs. 71.0/mL; p=0.11). At 30 days after stroke, however, VCAM-1 peaked (628.1/mL vs. 869.1/mL; p<0.01) but there was no significant change in endothelial progenitor cells (90/mL vs. 78/mL; p<0.34). At 180 days after stroke, circulating endothelial cells and VWF decreased, compared to baseline. Cultured endothelial progenitor cells from controls and myocardial infarction patients had endothelial phenotype characteristics and exhibited functional differences in adhesion and Ca(2+) influx, but not in proliferation and vasculogenesis. In myocardial infarction patients, VCAM-1 levels and mobilization of endothelial progenitor cells peaked at 30 days after the ischemic event. Although a similar VCAM-1 kinetic was observed in stroke patients, endothelial progenitor cells did not increase. Endothelial progenitor cells had mature endothelial capabilities in vitro.


Assuntos
Células Progenitoras Endoteliais/metabolismo , Infarto do Miocárdio/metabolismo , Acidente Vascular Cerebral/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Contagem de Células , Células Cultivadas , Células Endoteliais/metabolismo , Células Progenitoras Endoteliais/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/etiologia , Fenótipo , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Molécula 1 de Adesão de Célula Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologia , Fator de von Willebrand/metabolismo
10.
Eur Heart J ; 35(23): 1541-50, 2014 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-24682844

RESUMO

AIMS: The aim of this study was to assess the relationship between sex and clinical outcomes and treatment-related complications in patients with ST-elevation or non-ST-elevation acute coronary syndromes (ACS) randomized to treatment with ticagrelor or clopidogrel in the PLATelet inhibition and patient Outcomes (PLATO) trial. METHODS: The associations between sex subgroup and the primary composite outcomes, secondary outcomes, and major bleeding endpoints as well as interaction of sex subgroup with treatment effects were analysed using Cox proportional-hazards models. RESULTS: Sex was not significantly associated with the probability of the primary composite endpoint [adjusted hazard ratio (HR): 1.02 (0.91-1.16)], or other adverse cardiovascular endpoints. Ticagrelor was similarly more effective than clopidogrel in reducing rates of the primary endpoint in women 11.2 vs. 13.2% [adjusted HR: 0.88 (0.74-1.06)] and men 9.4 vs. 11.1% [adjusted HR: 0.86 (0.76-0.97)] (interaction P-value 0.78), all-cause death in women 5.8 vs. 6.8% [adjusted HR: 0.90 (0.69-1.16)] and men 4.0 vs. 5.7% [adjusted HR: 0.80 (0.67-0.96)] (interaction P-value 0.49), and definite stent thrombosis in women 1.2 vs. 1.4% [adjusted HR: 0.71 (0.36-1.38)] and men 1.4 vs. 2.1% [adjusted HR: 0.63 (0.45-0.89)] (interaction P-value 0.78). The treatments did not differ for PLATO-defined overall major bleeding complications in women [adjusted HR: 1.01 (0.83-1.23)] or men [adjusted HR: 1.10 (0.98-1.24)]. Sex had no significant association with these outcomes (interactions P = 0.43-0.88). CONCLUSION: Female sex is not an independent risk factor for adverse clinical outcomes in moderate-to-high risk ACS patients. Ticagrelor has a similar efficacy and safety profile in men and women.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Adenosina/análogos & derivados , Inibidores da Agregação de Plaquetas/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Ticlopidina/análogos & derivados , Adenosina/administração & dosagem , Adenosina/efeitos adversos , Idoso , Clopidogrel , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Oclusão de Enxerto Vascular/prevenção & controle , Hemorragia/induzido quimicamente , Humanos , Masculino , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/efeitos adversos , Estudos Prospectivos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Recidiva , Fatores Sexuais , Stents , Acidente Vascular Cerebral/etiologia , Ticagrelor , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos , Resultado do Tratamento
11.
Exp Gerontol ; 55: 1-11, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24607550

RESUMO

Senescence accelerated mice (SAM) are susceptible to developing vascular dysfunction and remodeling. Food intake and type of diet have also been identified as determining factors in vascular remodeling. However, the interplay between senescence and diet in vascular remodeling is largely unknown. We aimed to analyze structure of large (aorta) and small (mesenteric; MA) arteries from seven-month-old SAM prone (SAMP8) and resistant (SAMR1) mice that received a Western-type high-fat diet (WD; 8weeks). Aortic structure was assessed by morphometric analysis of hematoxylin and eosin-stained cross sections, and collagen content by qRT-PCR, immunofluorescence and picrosirius red. In MAs, structural and mechanical properties were measured by pressure myography; elastin and collagen content by qRT-PCR and immunofluorescence; nuclei distribution by confocal microscopy; and apoptosis by qRT-PCR and TUNEL assay. In aorta, wall thickness (WT), but not cross-sectional area (CSA), was increased by senescence, and WD only increased WT in SAMR1. WD intake, but not senescence, was associated with increased collagen deposition. In MAs, senescence diminished WT and CSA, without altering collagen and elastin deposition, reduced the number of MA wall cells, and increased pro apoptotic activation. WD consumption promoted in SAMR1 the same remodeling observed with senescence, while in SAMP8 the senescence-associated changes remained unaffected. The mechanisms involved in WD-induced MA remodeling in SAMR1 mimicked those observed in senescence per se. Our study reveals qualitatively different remodeling in aortas and MAs from senescent mice. Consumption of a WD induced remodeling of the SAMR1 vasculature similar to that induced by senescence, while it did not promote any further alteration in the latter. Therefore, we propose that increased consumption of fat-enriched diets could promote accelerated senescence of the non-senescent vasculature, although it does not exacerbate vascular remodeling during senescence.


Assuntos
Senilidade Prematura/fisiopatologia , Envelhecimento/fisiologia , Dieta Ocidental , Remodelação Vascular/fisiologia , Envelhecimento/metabolismo , Envelhecimento/patologia , Senilidade Prematura/metabolismo , Senilidade Prematura/patologia , Fenômenos Fisiológicos da Nutrição Animal/fisiologia , Animais , Aorta Torácica/metabolismo , Aorta Torácica/patologia , Aorta Torácica/fisiopatologia , Apoptose/fisiologia , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Dieta Hiperlipídica , Matriz Extracelular/metabolismo , Feminino , Artérias Mesentéricas/metabolismo , Artérias Mesentéricas/patologia , Artérias Mesentéricas/fisiopatologia , Camundongos , Camundongos Endogâmicos , Músculo Liso Vascular/patologia
15.
Eur Heart J Acute Cardiovasc Care ; 3(2): 132-40, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24448752

RESUMO

BACKGROUND: Few studies have addressed the additional value of B-type natriuretic peptide (BNP) on risk stratification in non-ST-elevation acute coronary syndrome (NSTE-ACS). We aimed to evaluate whether BNP levels provide additional improvement on discrimination and reclassification of patients at risk of mortality during admission and follow up after a NSTE-ACS. METHODS: BNP levels were measured 24-96 hours post admission in 600 patients with a NSTE-ACS. The incremental predictive value of including BNP into the multivariate models with the highest predictive accuracy for mortality during admission (logistic regression) and follow up (Cox regression) and over the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events (GRACE) risk scores was assessed using calibration, discrimination (area under the ROC curve (AUC) and Harrell's C statistic), and reclassification measures (net reclassification improvement (NRI) and index discrimination improvement (IDI)). RESULTS: A total of 19 (3.2%) patients died during admission and 29 (4.1%) during follow up (median 13.4 months). BNP was independently associated with mortality during admission (OR 3.56, 95% CI 1.75-7.23) and improved discrimination (AUC 0.95 vs. 0.92, p=0.01) and reclassification (NRI 72% and IDI 8%, p<0.05 for both). Similarly, BNP was an independent predictor of mortality during follow up (HR 2.46, 95% CI 1.94-3.12) and provided additional discriminative value (Harrell's C 0.86 vs. 0.84, p=0.04). Similarly, BNP demonstrated additional value above the TIMI and GRACE scores. CONCLUSIONS: Determination of BNP 24-96 hours after a NSTE-ACS improved discrimination of patients at risk for mortality during admission and follow up.


Assuntos
Síndrome Coronariana Aguda/mortalidade , Peptídeo Natriurético Encefálico/metabolismo , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/terapia , Idoso , Biomarcadores/metabolismo , Feminino , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Curva ROC , Medição de Risco
17.
Eur J Clin Invest ; 44(1): 83-92, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24350923

RESUMO

BACKGROUND: Stem cell therapy offers a promising approach to reduce the long-term mortality rate associated with heart failure after acute myocardial infarction (AMI). To date, in vivo translational studies have not yet fully studied the immune response to allogeneic adipose tissue-derived mesenchymal stem cells (ATMSCs). We analysed the immune response and the histological and functional effects of allogeneic ATMSCs in a porcine model of reperfused AMI and determine the effect of administration timing. DESIGN: Pigs that survived AMI (24/26) received intracoronary administration of culture medium after reperfusion (n = 6), ATMSCs after reperfusion (n = 6), culture medium 7 days after AMI (n = 6) or ATMSCs 7 days after AMI (n = 6). At 3-week follow-up, cardiac function, alloantibodies and histological analysis were evaluated. RESULTS: Administration of ATMSCs after reperfusion and 7 days after AMI resulted in similar rates of cell engraftment; some of those cells expressed endothelial, smooth muscle and cardiomyogenic cell lineage markers. Delivery of ATMSCs after reperfusion compared with that performed at 7 days was more effective in increasing: vascular density (249 ± 64 vs. 161 ± 37 vessels/mm2; P < 0.01), T lymphocytes (1 ± 0.4 vs. 0.4 ± 0.3% of area CD3(+) ; P < 0.05) and expression of vascular endothelial growth factor (VEGF; 32 ± 7% vs. 20 ± 4% of area VEGF(+) ; P < 0.01). Allogeneic ATMSC-based therapy did not change ejection fraction but generated alloantibodies. CONCLUSIONS: The present study is the first to demonstrate that allogeneic ATMSCs elicit an immune response and, when administered immediately after reperfusion, are more effective in increasing VEGF expression and neovascularization.


Assuntos
Tecido Adiposo/citologia , Transplante de Células-Tronco Mesenquimais , Infarto do Miocárdio/terapia , Animais , Modelos Animais de Doenças , Sobrevivência de Enxerto , Células-Tronco Mesenquimais/metabolismo , Microscopia Confocal , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Volume Sistólico , Suínos , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/metabolismo
18.
Heart Lung Circ ; 23(3): 273-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24021236

RESUMO

BACKGROUND: Heart failure with preserved ejection fraction (HFPEF) is the most prevalent form of heart failure in outpatients. Yet, the pathophysiology of this syndrome is unclear and pharmacological treatment does not improve prognosis. Because breathlessness during activities of daily living is the most frequent complaint of patients with HFPEF, we hypothesised that lung function may be often abnormal in these patients due to either a direct effect of HFPEF and/or shared risk factors. In this study we explore the frequency, type and severity of lung function abnormalities in HFPEF. METHODS: We measured forced spirometry, static lung volumes, pulmonary diffusing capacity (DL(CO)) and arterial blood gases in 69 outpatients with newly diagnosed symptomatic HFPEF. RESULTS: We found that 94% of the patients showed abnormalities in at least one of the lung function measurements obtained: spirometry was abnormal in 59%, DL(CO) in 83% and arterial hypoxaemia was present in 62%. Their severity varied between patients, they were more prevalent in patients with NYHA functional class III/IV, and most often they were undiagnosed and untreated. CONCLUSIONS: Lung function abnormalities are very frequent in HFPEF patients. A greater awareness among clinicians may contribute to improve their management and health status.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Pulmão/fisiopatologia , Volume Sistólico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Projetos Piloto , Testes de Função Respiratória , Estudos Retrospectivos
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