RESUMO
BACKGROUND: The association of platelet and monocyte activity markers with long-term mortality was assessed in hemodialysis (HD) patients. METHODS: In 41 HD patients (25 male, 16 female), surface expression of CD40L and CD62P on platelets, tissue factor (TF) binding on monocytes, and platelet-monocyte aggregates were measured by flow cytometry. Plasma levels of MCP-1, IL-6, TNFα, and soluble CD40L were analyzed by enzyme linked immunosorbent assay. Cox proportional hazard regression analyses and Kaplan-Meier curve were calculated. The predefined endpoint was all-cause mortality. RESULTS: The study follow-up was 11.54 years. Thirty-one patients (75.6%) died within the study period. Mean patient survival after study inclusion was 5.45 +/- 4.24 years. TF on monocytes above the median of the study population was significantly and independently associated with total mortality (HR (95% CI) 3.45 (1.32 - 9.07); p = 0.01). Cumulative mortality in patients with TF on monocytes above median was significantly higher compared to pa-tients with TF on monocytes below median value (log rank p < 0.01). Platelet-monocyte aggregates, the expression of CD40L and CD62P on platelets, and plasma levels of sCD40L, IL-6, MCP-1, and TNFα were not significantly correlated with mortality. CONCLUSIONS: The present study confirms a high mortality in ESRD patients. TF binding on monocytes was significantly correlated with increased mortality and may identify a subgroup of patients at higher risk.
Assuntos
Plaquetas/metabolismo , Falência Renal Crônica , Monócitos/metabolismo , Idoso , Aterosclerose , Feminino , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária , Diálise Renal , Tromboplastina/análise , Tromboplastina/metabolismoRESUMO
BACKGROUND AND AIMS: The CD40-CD40 Ligand (CD40L) system has an important role in vascular inflammation. For this reason, we assessed the association of soluble CD40L with cardiovascular and all-cause mortality in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. METHODS: Plasma levels of sCD40L were determined in 2759 persons using an enzyme immunoassay. Cox proportional hazard regressions were performed to evaluate the association between plasma concentration of sCD40 ligand and short-term (12 months) and long-term (10 years) mortality. Subpopulation analyses were conducted in seven different risk groups. Cox regression models were adjusted for traditional risk factors. RESULTS: The present study did not reveal significant association between sCD40L plasma levels and all-cause mortality, as well as cardiovascular mortality at one-year follow-up. In selected subgroups only, significant association between elevated sCD40L plasma levels and short-term all-cause and cardiovascular mortality could be observed. With regard to long-term all-cause and cardiovascular mortality analyses, no significant correlation with increased plasma levels of sCD40L could be detected, neither overall nor in any subgroup. CONCLUSIONS: Soluble sCD40L is not associated with cardiovascular and all-cause mortality in this large cohort. Only in selected patient subgroups elevated levels of sCD40L correlate with short-term mortality but this correlation disappears in long-term analysis.
Assuntos
Ligante de CD40/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Causas de Morte , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Regulação para CimaRESUMO
PURPOSE: Dronedarone is a multichannel-blocking antiarrhythmic drug for the treatment of atrial fibrillation. Observational data hypothesized a cardioprotective effect. In an in vitro endothelial cell-platelet model, we evaluated the molecular atheroprotective effects of dronedarone. METHODS: Following a 24-h incubation of human umbilical vein endothelial cells (HUVECs) with dronedarone (concentration 50, 100, and 150 ng/mL), they were then stimulated for 1 h with lipopolysaccharide (LPS) and were subsequently incubated in direct contact with thrombin-activated platelets. After incubation, the expression of CD40L and CD62P on platelets, and the expression of ICAM-1, VCAM-1, urokinase-type plasminogen activator receptor (uPAR), and membrane type 1 matrix metalloproteinase (MT1-MMP) on endothelial cells were measured by flow cytometry. RESULTS: Preincubation with 150 ng/mL of dronedarone reduced the expression of uPAR on endothelial cells after proinflammatory stimulation with LPS and also by direct endothelial contact with activated platelets (p = 0.0038). In contrast, the expression of CD40L and CD62P on platelets after proinflammatory stimulation with thrombin was significantly increased through direct preincubation with 50/100/150 ng/mL of dronedarone. However, dronedarone had no effects on the expression of MT1-MMP and ICAM-1 in HUVECs. CONCLUSION: In this in vitro analysis, dronedarone directly increased platelet activation but showed significant direct effects on endothelial cells and indirect effects on platelets on selected markers of atherosclerosis.
Assuntos
Aterosclerose/tratamento farmacológico , Plaquetas/efeitos dos fármacos , Fármacos Cardiovasculares/farmacologia , Dronedarona/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Ativação Plaquetária/efeitos dos fármacos , Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Aterosclerose/metabolismo , Plaquetas/metabolismo , Ligante de CD40/metabolismo , Células Cultivadas , Citoproteção , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Lipopolissacarídeos/farmacologia , Selectina-P/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: In hemodialysis (HD) patients cardiovascular events represent the predominant cause of mortality. Since platelet and monocyte activity markers play an important role in cardiovascular mortality, this study assessed the influence of HD on these markers. METHODS: Forty one HD patients (25 male, 16 female) were included. Blood samples were obtained before and after a single HD session at baseline and again after an elapsed period of 114 ± 21 days (91-175 days) on maintenance hemodialysis. Surface expression of CD40L and CD62P on platelets, tissue factor binding on monocytes and platelet-monocyte aggregates were measured by flow cytometry. Plasma levels of monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFa) and soluble CD40L were analyzed by enzyme linked immunosorbent assay. RESULTS: Tissue factor on monocytes was significantly increased after a single HD session at baseline (p = 0.041), whereas platelet-monocyte aggregates, the expression of CD40L and CD62P on platelets did not change significantly. After a mean of 114 ± 21 days of HD therapy, tissue factor on monocytes (p < 0.0001), platelet-monocytes aggregates (p < 0.0001), plasma levels of MCP-1 (p = 0.012) and TNFa (p = 0.046) were significantly decreased compared to baseline values. In contrast, platelet surface expression of CD40L and CD62P as well as plasma levels of sCD40L and IL-6 were not attenuated significantly. There was no significant correlation detected between the markers examined and the cumulative time on hemodialysis. CONCLUSIONS: Platelet and monocyte activity markers assessed in this study do not appear to be significantly increased by HD therapy. Therefore, these markers probably cannot be accountable for increased cardiovascular mortality in chronic HD patients.
Assuntos
Aterosclerose/metabolismo , Plaquetas/metabolismo , Falência Renal Crônica/terapia , Monócitos/metabolismo , Ativação Plaquetária , Diálise Renal , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Biomarcadores/metabolismo , Quimiocina CCL2/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Seguimentos , Alemanha/epidemiologia , Humanos , Incidência , Interleucina-6/metabolismo , Falência Renal Crônica/complicações , Falência Renal Crônica/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida/tendências , Fatores de TempoRESUMO
PURPOSE: The predominant cause of mortality in dialysis patients are cardiovascular events. Platelet and monocyte activity markers play an important role in cardiovascular mortality and were assessed and related to dialysis quality criteria in haemodialysis (HD) and peritoneal dialysis (PD) patients. METHODS: For this prospective comparative study, HD patients (n = 41) and PD patients (n = 10) were included. In whole blood samples, surface expression of CD62P and CD40L on platelets, tissue factor binding on monocytes, and platelet-monocyte aggregates were measured by flow cytometry. Plasma levels of MCP-1, IL-6, TNFα, and soluble CD40L were analysed by enzyme-linked immunosorbent assay. RESULTS: Haemodialysis patients showed a significantly higher CD62P expression on platelets (p = 0.017), significantly higher amount of platelet-monocyte aggregates (p < 0.0001), and significantly more tissue factor binding on monocytes (p < 0.0001) compared to PD patients. In PD patients, a significant correlation between Kt/V and platelet CD40L expression (r = 0.867; 0.001) and between Kt/V and platelet CD62P expression (r = 0.686; p = 0.028) was observed, while there was no significant correlation between Kt/V and tissue factor binding on monocytes and platelet-monocyte aggregates, respectively. CONCLUSION: Platelet and monocyte activity markers are higher in HD patients in comparison with those in PD patients, possibly suggesting a higher risk of cardiovascular morbidity and mortality.
Assuntos
Aterosclerose/metabolismo , Plaquetas/metabolismo , Monócitos/metabolismo , Idoso , Ligante de CD40/metabolismo , Quimiocina CCL2/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal , Fator de Necrose Tumoral alfa/metabolismoRESUMO
PURPOSE: Lipid lowering therapy constitutes the basis of cardiovascular disease therapy. The purpose of this study was to investigate effects of ezetimibe, a selective inhibitor of intestinal cholesterol absorption, on platelets and endothelial cells in an in vitro endothelial cell model. METHODS: After a 24h incubation period with ezetimibe (concentrations 1, 50, 100 and 1000ng/ml), human umbilical vein endothelial cells (HUVEC) were stimulated for 1h with lipopolysaccharide (LPS) and were then incubated in direct contact with activated platelets. Following this, the expression of CD40L and CD62P on platelets, and the expression of ICAM-1, VCAM-1, uPAR, and MT1-MMP on endothelial cells were measured by flow cytometry. Supernatants were analysed by enzyme linked immunosorbent assay for soluble MCP-1, IL-6 and MMP-1. RESULTS: The increased expression of uPAR on endothelial cells by proinflammatory stimulation with LPS and by direct endothelial contact with activated platelets was significantly reduced through pre-incubation with 100ng/ml and 1000ng/ml ezetimibe (p<0.05). Platelets directly incubated with ezetimibe but without endothelial cell contact showed significantly reduced CD62P and CD40L surface expression (p<0.05). Ezetimibe had no significant effects on HUVEC expression of MT1-MMP, ICAM-1 and VCAM-1 and on CD40L expression on platelets in direct contact with endothelial cells. Levels of soluble IL-6 in HUVEC supernatants were significantly lower after pre-incubation with ezetimibe. CONCLUSION: In this in vitro analysis, ezetimibe directly attenuates platelet activation and has significant endothelial cell mediated effects on selected markers of atherosclerosis.
Assuntos
Ezetimiba/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Ativação Plaquetária/efeitos dos fármacos , Receptores de Ativador de Plasminogênio Tipo Uroquinase/antagonistas & inibidores , Receptores de Ativador de Plasminogênio Tipo Uroquinase/biossíntese , Anticolesterolemiantes/farmacologia , Células Cultivadas , Relação Dose-Resposta a Droga , Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Ativação Plaquetária/fisiologiaAssuntos
Molécula 1 de Adesão Intercelular/sangue , Infarto do Miocárdio/sangue , Fibrilação Ventricular/sangue , Biomarcadores/sangue , Angiografia Coronária , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , RNA Mensageiro/sangue , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Fatores de Risco , Fibrilação Ventricular/etiologiaRESUMO
BACKGROUND: TSP-1 is a vasoconstrictive protein, which is released from both endothelium and cardiomyocytes during ischemia and promotes platelet aggregation and adhesion to subendothelial layers in atherosclerotic lesions. During myocardial ischemia and reperfusion, TSP-1 disturbs local microcirculation by disrupting both NO-signaling as well as VEGF-pathways by activation of CD47 and CD36. Furthermore, activation of TGF-ß might induce excessive fibrosis after infarction. It was assumed that TSP-1 is washed out after successful coronary reperfusion. In this study, we examined circulating TSP-1 post emergency PCI as a risk factor for major adverse cardiac events after STEMI with and without ventricular fibrillation. METHODS: TSP-1 levels in platelet poor plasma were measured in 54 patients after ST-elevation myocardial infarction. Major adverse cardiac events were monitored for 426 days. RESULTS: Patients with decreased TSP levels after coronary stenting showed a significantly higher risk for MACE than patient with higher TSP levels (TSP-1[d0]: n = 46, no MACE = 16.38 ± 1.98 ug/mL vs. MACE 7.11 ± 1.54 ug/mL; p = 0.003). Kaplan-Meyer-analysis for MACE showed a better outcome above 10 ug/mL (p = 0.02). For MACE later than 3 months post-STEMI, the corresponding Kaplan-Meier-analysis yielded a p-value of 0.01. The number needed to diagnose for late MACE was 2.158. CONCLUSION: Low plasma levels of TSP1 after PCI are associated with MACE. Due to its procoagulant effects and dysregulation of microvascular tone, adequately powered prospective studies are warranted to test the impact of TSP-1 on cardiac microcirculation, endothelial function and remodeling. TSP-1 might serve as a new diagnostic and therapeutic approach in cardiovascular disease.
Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/sangue , Infarto do Miocárdio/sangue , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Biomarcadores/sangue , Circulação Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reperfusão Miocárdica/efeitos adversos , Reperfusão Miocárdica/métodos , Fatores de Risco , Stents/efeitos adversos , Resultado do TratamentoRESUMO
AIM: To investigate effects of ethanol on activity markers of atherosclerosis in an in vitro endothelial cell model. METHODS: After 24 h incubation with ethanol (0.0095%), human umbilical vein endothelial cells were stimulated for 1 h with lipopolysaccharide, and were then incubated in direct contact with activated platelets. Following this incubation, the expression of CD40L and CD62P on platelets, and the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), urokinase plasminogen activator receptor (uPAR), and membrane-type 1 matrix metalloproteinase (MT1-MMP) on endothelial cells were measured by flow cytometry. RESULTS: The increased expression of VCAM-1 and uPAR on endothelial cells by proinflammatory stimulation with activated platelets was significantly reduced through pre-incubation with ethanol (P < 0.05). Furthermore, platelets in direct contact with ethanol and with endothelial cells pre-incubated in ethanol showed a significant reduction in their CD40L expression (P < 0.05). Ethanol had no significant effect on ICAM-1 and MT1-MMP expression on endothelial cells. CONCLUSION: Ethanol directly attenuates platelet activation and has significant endothelial cell-mediated effects on selected markers of atherosclerosis in vitro. These findings underline possible protective effects of ethanol on atherosclerosis.
RESUMO
BACKGROUND: In addition to their cholesterol lowering ability, statins have proven pleiotropic effects in the cardiovascular system. Chronic inflammation with interactions between platelets and endothelial cells leads to an upregulation of activity markers of atherosclerosis. The purpose of this study was to investigate the effects of simvastatin and atorvastatin on platelets and endothelial cells in an in vitro endothelial cell model. METHODS AND RESULTS: After a 24 h incubation period with either simvastatin or atorvastatin (1 µmol/L), human umbilical vein endothelial cells were stimulated for 1 h with lipopolysaccharide (LPS), and were then incubated in direct contact with activated platelets. Platelet surface expression of CD40L and CD62P and expression of ICAM-1, VCAM-1, uPAR and MT1-MMP on endothelial cells were measured by flow cytometry. Supernatants were analyzed by ELISA for soluble MMP-1. The increased expression of VCAM-1 and uPAR on endothelial cells by stimulation with LPS and by direct contact with activated platelets was significantly reduced to a similar extent through pre-incubation with both atorvastatin and simvastatin (p < 0.05). Platelets without endothelial cell contact, but in direct contact with either statin, showed similar significant reductions in surface expression of CD40L (p < 0.005). CONCLUSIONS: These effects may explain the ability of statins to reduce the progression of atherosclerosis in addition to their cholesterol-lowering properties.
Assuntos
Anti-Inflamatórios/farmacologia , Plaquetas/efeitos dos fármacos , Ligante de CD40/metabolismo , Ácidos Heptanoicos/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Pirróis/farmacologia , Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Sinvastatina/farmacologia , Molécula 1 de Adesão de Célula Vascular/metabolismo , Atorvastatina , Biomarcadores/metabolismo , Plaquetas/metabolismo , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Lipopolissacarídeos/farmacologia , Metaloproteinase 14 da Matriz/metabolismo , Selectina-P/metabolismo , Ativação Plaquetária/efeitos dos fármacos , Trombina/metabolismoAssuntos
Ácidos Graxos não Esterificados/sangue , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Peptídeo Natriurético Encefálico/sangue , Norepinefrina/sangue , Fragmentos de Peptídeos/sangue , Fibrilação Ventricular/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Estudos ProspectivosRESUMO
BACKGROUND: Interactions between platelets and endothelial cells under inflammatory conditions lead to an increased expression of various activity markers of atherosclerosis in the vessel wall. The purpose of this study was to investigate possible protective effects of nicotinic acid in an in vitro endothelial cell model. METHODS: After a 24-hour incubation period with nicotinic acid (1 mmol/l), human umbilical vein endothelial cells were stimulated for 1 h with lipopolysaccharide and were then incubated in direct contact with activated platelets. Following this incubation, the expression of CD40L and CD62P on platelets and the expression of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, uPAR, and MT1-MMP on endothelial cells were measured by flow cytometry. Supernatants were analyzed by ELISA for soluble MCP-1 and MMP-1. RESULTS: The increased expression of VCAM-1 on endothelial cells by proinflammatory stimulation with activated platelets was significantly reduced through preincubation with nicotinic acid (P<.05). Furthermore, platelets in direct contact with preincubated endothelial cells showed a significant reduction in their CD62P and CD40L expression when compared to platelets incubated with untreated endothelial cells (P<.05). Treatment with nicotinic acid did not have a significant effect on ICAM-1, uPAR, and MT1-MMP expression on endothelial cells. Levels of soluble MCP-1 and MMP-1 in supernatants were lower after preincubation with nicotinic acid. CONCLUSION: Nicotinic acid inhibits platelet activation after platelets contacted nicotinic acid treated endothelial cells and inhibits VCAM-1 expression on human endothelial cells under inflammatory conditions. These findings suggest a possible pleiotropic therapeutic relevance of nicotinic acid in atherosclerosis.
Assuntos
Plaquetas/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Niacina/farmacologia , Antígenos CD/metabolismo , Biomarcadores/metabolismo , Plaquetas/metabolismo , Células Cultivadas , Técnicas de Cocultura , Citocinas/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Lipopolissacarídeos/farmacologia , Ativação Plaquetária/efeitos dos fármacos , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
An upregulation of platelet CD40 ligand (CD40L) and CD62P has been described in atherosclerotic cardiovascular diseases and among patients with acute cerebral ischemia. Correlation between platelet and monocyte activation and the etiology of ischemic stroke were examined in 41 patients with acute ischemic stroke. Compared to 10 controls, all patients with stroke showed a significantly elevated platelet expression of CD40L (P < .001) and had significantly higher amounts of platelet-monocyte aggregates (P = .002). Plasma levels of interleukin 7 were significantly lower in patients with stroke compared to controls (P = .006). Patients with small artery disease had a significantly higher platelet CD40L expression than patients with cardioembolic stroke (P = .029). Plasma levels of soluble CD40L were significantly higher in patients with large artery disease compared to patients with cardioembolic stroke (P = .047). In conclusion, patients with acute ischemic stroke show an upregulation of platelet CD40L and an activation of cellular coagulation with highest activation in the large artery disease subgroup.
Assuntos
Plaquetas/metabolismo , Isquemia Encefálica/sangue , Monócitos/metabolismo , Agregação Plaquetária , Acidente Vascular Cerebral/sangue , Idoso , Idoso de 80 Anos ou mais , Plaquetas/patologia , Isquemia Encefálica/patologia , Ligante de CD40/biossíntese , Feminino , Humanos , Interleucina-7/sangue , Masculino , Pessoa de Meia-Idade , Monócitos/patologia , Selectina-P/biossíntese , Acidente Vascular Cerebral/patologia , Regulação para CimaRESUMO
Patients with Takotsubo cardiomyopathy (TC) often present with symptoms similar to those of myocardial infarction (MI). We analyzed blood concentrations of mediators of inflammation and platelet- and monocyte-activity markers in patients with TC and MI for significant differences. Clinical data of patients with TC (n = 16) and acute MI (n = 16) were obtained. Serial blood samples were taken at the time of hospital admission (t(0)), after 2-4 days (t(1)) and after 4-7 weeks (t(2)), respectively. Plasma concentrations of interleukin (IL)-6, IL-7, soluble CD40 ligand (sCD40L), and monocyte chemotactic protein 1 (MCP-1) were determined with an ELISA. Tissue factor binding on monocytes, platelet-activation marker CD62P, platelet CD40-ligand (CD40L), and platelet-monocyte aggregates were measured using flow cytometry. Expression of CD62P on platelets and IL-6 plasma levels were significantly lower in patients with TC compared to MI at the time of hospital admission. IL-7 plasma levels were significantly elevated in patients with TC compared to patients with MI at 2-4 days after hospital admission. No significant differences were observed concerning sCD40L and MCP-1 plasma levels, tissue factor binding on monocytes, CD40L expression on platelets, and platelet-monocyte aggregates at any point in time. Our results indicate that inflammatory mediators and platelet-activity markers contribute to the differences in the pathogenesis of MI and TC.
Assuntos
Plaquetas/imunologia , Mediadores da Inflamação/sangue , Monócitos/imunologia , Infarto do Miocárdio/imunologia , Ativação Plaquetária , Cardiomiopatia de Takotsubo/imunologia , Trombose/imunologia , Idoso , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Admissão do Paciente , Estudos Prospectivos , Cardiomiopatia de Takotsubo/sangue , Trombose/sangue , Fatores de TempoAssuntos
Apêndice Atrial/diagnóstico por imagem , Neoplasias Cardíacas/diagnóstico por imagem , Histiocitoma Fibroso Maligno/diagnóstico por imagem , Neoplasias Cutâneas/cirurgia , Idoso , Ecocardiografia Transesofagiana , Cotovelo , Feminino , Neoplasias Cardíacas/secundário , Histiocitoma Fibroso Maligno/secundário , Humanos , Metástase Neoplásica , Neoplasias Cutâneas/patologiaRESUMO
OBJECTIVE: Inflammatory conditions contribute to increased expression of various activity markers in platelets and endothelial cells, leading to atherosclerotic changes in the vascular wall. The objective of this study was to investigate possible protective effects of 1α,25-dihydroxyvitamin D3 in an endothelial cell model. METHODS: After a 24-hour incubation with 1α,25-dihydroxyvitamin D3, human umbilical vein endothelial cells were stimulated with lipopolysaccharide (LPS) and incubated in direct contact with platelets. The expression of CD40L and CD62P in platelets, the expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 (VCAM-1), the urokinase receptor uPAR and membrane type 1 matrix metalloproteinase (MT1-MMP) in endothelial cells and endothelial cell reactive oxygen species generation were measured by flow cytometry. Endothelial nitric oxide synthase was analyzed by Western blot. RESULTS: The increased expression of VCAM-1 and MT1-MMP in endothelial cells by proinflammatory stimulation with LPS and by direct contact with activated platelets was significantly reduced through preincubation with 1α,25-dihydroxyvitamin D3. Platelets in direct contact with preincubated endothelial cells showed significantly reduced CD62P expression when compared to platelets incubated with untreated endothelial cells. CONCLUSIONS: 1α,25-Dihydroxyvitamin D3 attenuates platelet activation and the expression of VCAM-1 and MT1-MMP in human endothelial cells and could have early therapeutic relevance in atherosclerotic diseases.
Assuntos
Aterosclerose/prevenção & controle , Calcitriol/metabolismo , Metaloproteinase 14 da Matriz/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo , Biomarcadores , Plaquetas , Ligante de CD40 , Células Endoteliais , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Selectina-P , Veias UmbilicaisRESUMO
BACKGROUND: In a recently published genome-wide association study (GWAS), three single nucleotide polymorphisms (SNPs) (rs2824292, rs1353342, rs12090554) were significantly associated with increased susceptibility for ventricular fibrillation (VF) during acute myocardial infarction (AMI). The association of rs2824292 could be confirmed in a second cohort. Both cohorts were from the Netherlands. We aimed to replicate this association in a German cohort of AMI patients with or without VF. METHODS: We included a German cohort of 90 individuals with AMI and VF (cases) and 167 AMI individuals without VF and used Taqman assays for SNP typing. RESULTS: None of the loci showed evidence for a statistically significant association with VF. The observed genotype frequencies of the three loci were in Hardy-Weinberg equilibrium, which essentially excludes genotyping errors. CONCLUSIONS: In contrast to the data from the Netherlands, we could not detect a significant association of the rs2824292 locus and risk of VF during AMI in our German cohort. Differences in recruitment and clinical phenotypes between the Dutch and German cohorts may underlie different genotype associations.
Assuntos
Cromossomos Humanos Par 21/genética , Infarto do Miocárdio/complicações , Polimorfismo de Nucleotídeo Único/genética , Fibrilação Ventricular/complicações , Fibrilação Ventricular/genética , Doença Aguda , Estudos de Coortes , Feminino , Frequência do Gene , Alemanha , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We aimed to determine the diagnostic performance of biomarkers in predicting myocardial fibrosis assessed by late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR) in patients with hypertrophic cardiomyopathy (HCM). LGE CMR was performed in 40 consecutive patients with HCM. Left and right ventricular parameters, as well as the extent of LGE were determined and correlated to the plasma levels of midregional pro-atrial natriuretic peptide (MR-proANP), midregional pro-adrenomedullin (MR-proADM), carboxy-terminal pro-endothelin-1 (CT-proET-1), carboxy-terminal pro-vasopressin (CT-proAVP), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and interleukin-8 (IL-8). Myocardial fibrosis was assumed positive, if CMR indicated LGE. LGE was present in 26 of 40 patients with HCM (65%) with variable extent (mean: 14%, range: 1.3-42%). The extent of LGE was positively associated with MR-proANP (r = 0.4; P = 0.01). No correlations were found between LGE and MR-proADM (r = 0.1; P = 0.5), CT-proET-1 (r = 0.07; P = 0.66), CT-proAVP (r = 0.16; P = 0.3), MMP-9 (r = 0.01; P = 0.9), TIMP-1 (r = 0.02; P = 0.85), and IL-8 (r = 0.02; P = 0.89). After adjustment for confounding factors, MR-proANP was the only independent predictor associated with the presence of LGE (P = 0.007) in multivariate analysis. The area under the ROC curve (AUC) indicated good predictive performance (AUC = 0.882) of MR-proANP with respect to LGE. The odds ratio was 1.268 (95% confidence interval 1.066-1.508). The sensitivity of MR-proANP at a cut-off value of 207 pmol/L was 69%, the specificity 94%, the positive predictive value 90% and the negative predictive value 80%. The results imply that MR-proANP serves as a novel marker of myocardial fibrosis assessed by LGE CMR in patients with HCM.
Assuntos
Fator Natriurético Atrial/sangue , Cardiomiopatia Hipertrófica/sangue , Imagem Cinética por Ressonância Magnética , Miocárdio/química , Adrenomedulina/sangue , Adulto , Idoso , Biomarcadores/sangue , Cardiomiopatia Hipertrófica/patologia , Cardiomiopatia Hipertrófica/fisiopatologia , Meios de Contraste , Endotelina-1/sangue , Feminino , Fibrose , Gadolínio DTPA , Alemanha , Glicopeptídeos/sangue , Humanos , Interleucina-8/sangue , Modelos Logísticos , Masculino , Metaloproteinase 9 da Matriz/sangue , Pessoa de Meia-Idade , Miocárdio/patologia , Razão de Chances , Valor Preditivo dos Testes , Precursores de Proteínas/sangue , Curva ROC , Volume Sistólico , Inibidor Tecidual de Metaloproteinase-1/sangue , Função Ventricular EsquerdaRESUMO
BACKGROUND: The widespread use of primary coronary intervention (PCI) has significantly improved the prognosis of men presenting with acute coronary syndromes, but the cardiovascular event rate among women has either levelled off or increased. The purpose of the present prospective study was to compare the clinical outcome of women and men presenting with ST-elevation myocardial infarction (STEMI) undergoing primary PCI with concomitant usage of GP IIb/IIIa inhibitors. METHODS: Between January 2006 and December 2007, 297 consecutive patients presenting with STEMI were prospectively included in this single center investigation. Overall, 82 (27.6%) women and 215 (72.4%) men were treated by PCI with additional bare metal stent implantation and a GP IIb/IIIa inhibitor. RESULTS: Women were significantly older (65 ± 10 vs 60 ± 12 years, p = 0.04), presented with a smaller reference luminal diameter (2.83 ± 0.51 vs 2.94 ± 0.43, p = 0.03) and had a higher prevalence of hypertension (68% vs 53%, p = 0.025) and obesity (30% vs 18%, p = 0.03). The incidence of major adverse cardiac events (MACE, defined as death, re-myocardial infarction, target lesion revascularization and coronary artery bypass graft) during long-term follow-up was similar in women and men (20% vs 26%, p = 0.29). Age, C-reactive protein, platelet count and cardiogenic shock were identified as independent predictors for MACE, whereas gender was not predictive. CONCLUSIONS: In this study, female gender did not emerge as an independent predictor for MACE, but women presenting with STEMI had a higher cardiovascular risk profile; this emphasizes the need for a more extensive therapeutic strategy. Combination therapy with primary PCI and GP IIb/IIIa inhibitors might mitigate gender-related differences in clinical outcomes.
Assuntos
Angioplastia Coronária com Balão , Angiografia Coronária , Infarto do Miocárdio/terapia , Inibidores da Agregação Plaquetária/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Idoso , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/instrumentação , Angioplastia Coronária com Balão/mortalidade , Doenças Cardiovasculares/etiologia , Distribuição de Qui-Quadrado , Feminino , Alemanha , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Metais , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/mortalidade , Estudos Prospectivos , Desenho de Prótese , Medição de Risco , Fatores de Risco , Fatores Sexuais , Stents , Fatores de Tempo , Resultado do TratamentoRESUMO
Platelets and monocytes play a pivotal role in the initiation and progression of large-vessel atherosclerosis. An up-regulation of various platelet and coagulation activation markers has been described in cardiovascular diseases and in patients with acute cerebral ischemia. In the present study the role of platelets and cellular coagulation activation in cerebral small-vessel disease (cSVD) was assessed. In 24 patients with cSVD but without established large-vessel disease, whole blood samples were obtained. Patients were divided into three subgroups (Fazekas 1, 2 and 3) according to extent of cSVD based on morphological magnetic resonance imaging criteria. Surface expression of CD40L and CD62P on platelets, tissue-factor exposition on monocytes and platelet-monocyte aggregates were measured with flow cytometry. Plasma levels of soluble CD40L, interleukin (IL)-6 and IL-7 were assessed by ELISA. Patients with cSVD show a significantly elevated expression of platelet CD40L (P < 0.001) and CD62P (P < 0.023), significantly elevated amounts of platelet-monocyte aggregates (P < 0.004), a significantly enhanced tissue-factor exposition on monocytes (P < 0.019) and significantly lower plasma levels of IL-7 compared to 10 healthy controls. However, this platelet and monocyte activation did not correlate with the severity of cSVD. Patients with cSVD show an up-regulation of the platelet CD40L and CD62P system and an activation of cellular coagulation which might contribute to the initiation and progression of cSVD.