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1.
Europace ; 19(8): 1288-1292, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-27702871

RESUMO

AIMS: Previous studies revealed that patients with Takotsubo cardiomyopathy (TTC) have a higher mortality rate than the general population. Supraventricular tachycardia is a well-known complication of TTC. This study was performed to determine the short- and long-term prognostic impact of atrial fibrillation associated with TTC patients. METHODS AND RESULTS: Our institutional database constituted a collective of 114 patients diagnosed with TTC from 2003 to 2015. The patients were divided into two groups according to the presence (n = 21, 18.4%) or absence (n = 93, 81.5%) of atrial fibrillation. The endpoint was a composite of in-hospital events (thromboembolic events and life-threatening arrhythmias), all-cause mortality, rehospitalization due to heart failure, stroke, and the recurrence of TTC. The in-hospital mortality, 30-day mortality, and long-term mortality were significantly higher in the atrial fibrillation group. Kaplan-Meier analysis indicated a significantly lower event-free survival rate over a mean follow-up of 3 years in the atrial fibrillation group than that in the non-atrial fibrillation group (log-rank, P < 0.01). In a multivariate cox regression analysis, atrial fibrillation (hazard ratio, HR 2.3, 95% confidence interval, CI: 1.1-4.9, P < 0.05) and EF ≤ 35% (HR 2.0, 95% CI: 1.1-3.8, P < 0.05) were the only independent predictors of a primary endpoint. CONCLUSION: Rates of in-hospital events and short- as well as long-term mortality were significantly higher in TTC patients suffering from atrial fibrillation compared with patients without atrial fibrillation.


Assuntos
Fibrilação Atrial/complicações , Cardiomiopatia de Takotsubo/complicações , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/mortalidade , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/terapia , Causas de Morte , Distribuição de Qui-Quadrado , Bases de Dados Factuais , Progressão da Doença , Intervalo Livre de Doença , Feminino , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Readmissão do Paciente , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Cardiomiopatia de Takotsubo/mortalidade , Cardiomiopatia de Takotsubo/fisiopatologia , Cardiomiopatia de Takotsubo/terapia , Fatores de Tempo
3.
Int J Cardiol ; 220: 371-5, 2016 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-27390957

RESUMO

OBJECTIVE: Takotsubo cardiomyopathy, also known as stress-induced cardiomyopathy (SCM) resembles a reversible cardiomyopathy that is characterized by localized wall motion abnormalities in the absence of stenotic coronary vascular disease. Patients typically present with apical ballooning of the left ventricle (LV), however the right ventricle (RV) is also affected in up to 50.0% of patients. Long-term prognosis of classical SCM resembles that of patients after ST elevation myocardial infarction. Data on long-term prognosis of biventricular compared to classical SCM is controversial. The aim of this study was therefore to analyze patients with biventricular SCM regarding in-hospital outcome and long-term prognosis. MATERIALS AND METHODS: 114 consecutive patients with SCM were retrospectively analyzed. 88 patients presented with classical SCM, 26 patients (22.8%) were diagnosed with biventricular SCM. Follow-up was conducted for a total of 4.4years. Mean age was 67.1years with 83.3% of patients being female. The primary endpoint was a composite of all-cause mortality, recurrence of SCM and re-hospitalization due to heart failure. RESULTS: Although patients with biventricular SCM presented with a tendency towards an increased rate of cardiogenic shock (30.8% vs. 15.9%; p=0.09) and significantly more usage of inotropic support upon hospital admission (34.6% vs. 13.6%; p=0.01), there was no difference concerning the primary endpoint in both groups (50.0% vs. 44.3%; p=0.31). Furthermore, there was no difference in mortality both in-hospital (7.7% vs. 7.9%; p=0.66) and during long-term follow-up (27.3% vs. 23.1%; p=0.46). CONCLUSION: Patients with biventricular SCM have the same in-hospital and long-term outcome compared to classical SCM.


Assuntos
Mortalidade Hospitalar/tendências , Cardiomiopatia de Takotsubo/diagnóstico por imagem , Cardiomiopatia de Takotsubo/mortalidade , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/mortalidade , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
4.
In Vivo ; 30(3): 213-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27107077

RESUMO

BACKGROUND: Cell-surface adhesion molecules regulate multiple intercellular and intracellular processes and play important roles in inflammation by facilitating leukocyte endothelial transmigration. Whether cardiomyocytes express surface-adhesion molecules related to inflammation and the effect of pro-inflammatory mediators remain unknown. MATERIALS AND METHODS: In the present study, the expression of different cell-adhesion molecules (CD11a, CD11b, CD31, CD62P, CD162, F11 receptor and mucosal vascular addressin cell adhesion molecule 1 (MADCAM1)) and the effect of pro-inflammatory mediators were investigated in an in vitro model of human cardiomyocytes. Cells were supplied as a primary culture of cardiac alpha actin-positive cells from human heart tissue. The cells were incubated for 24 h with 1 U/ml thrombin or 700 ng/ml lipopolysaccharide (LPS) or with a combination of both. The expression of the cell adhesion molecules was measured by flow cytometry. RESULTS: In cultured human cardiomyocytes, 22.8% of cells expressed CD31, 7.1% MADCAM1 and 2.6% F11R. CD11a, CD11b, CD62P and CD162 were expressed by fewer than 2% of the cells at baseline. CD31 expression increased on incubation of cardiomyocytes with thrombin by 26% (p<0.05) and with LPS by 26% (p=0.06). The combination of thrombin and LPS did not result in increased levels of CD31 (p>0.10). The pro-inflammatory agents LPS and thrombin had no effect on the expression of MADCAM1 and F11R. CONCLUSION: Inflammation-related cell-adhesion molecules CD31, MADCAM1 and F11R were shown to be expressed on the surface of human cardiomyocytes in an in vitro model. Incubation with LPS or thrombin resulted in increased expression of CD31, however, it did not modify the expression of the cell adhesion molecules MADCAM1 and F11R.


Assuntos
Moléculas de Adesão Celular/metabolismo , Lipopolissacarídeos/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Trombina/farmacologia , Actinas/metabolismo , Adulto , Antígeno CD11a/metabolismo , Antígeno CD11b/metabolismo , Células Cultivadas , Citometria de Fluxo , Humanos , Imunoglobulinas/metabolismo , Inflamação/metabolismo , Molécula A de Adesão Juncional/metabolismo , Glicoproteínas de Membrana/metabolismo , Mucoproteínas/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Selectina-P/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo
5.
J Geriatr Cardiol ; 13(11): 888-893, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28133464

RESUMO

BACKGROUND: Recurrence of takotsubo cardiomyopathy (TTC) is a well-known complication. However, current literature lists only a few isolated cases. We aimed to determine the incidence and clinical significance of recurrent TTC. METHODS & RESULTS: Our institutional database constituted a collective of 114 patients diagnosed with TTC since 2003. Close follow-up of these patients revealed a recurrence of TTC in seven of these (6.1%). The time interval between the index event and its recurrence varied between six months and six years. Arterial hypertension was more revealed in the recurrence group of TTC compared to non-recurrence group, (P = 0.02). Chronic obstructive pulmonary disease and/or asthma was more diagnosed in the recurrence group, (P = 0.04). Clinical events like right ventricular involvement, TTC related complications such as life-threatening arrhythmias, pulmonary congestion and in hospital death were observed more frequently in the recurrent episode. Over a mean follow-up of one year the mortality rate was similar in both groups. CONCLUSIONS: Recurrence of TTC within six years after index event is not an uncommon phenomenon. In the event of right ventricular involvement in the relapse phase, it might be associated with a higher complication rate. TTC recurrence should be the first differential diagnosis in patients with a past history of TTC.

8.
Mol Med Rep ; 10(4): 2039-44, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25051102

RESUMO

Mutations in the SCN5A gene encoding the Nav1.5 channel α-subunit are known to be risk factors of arrhythmia, including Brugada Syndrome and Long QT syndrome subtype 3. The present study focused on the role of SCN5A variants in the development of ventricular fibrillation (VF) during acute myocardial infarction (AMI). Since VF during AMI is the major cause of sudden death in the Western world, SCN5A mutations represent genetic risk factors for sudden death. By exon re-sequencing, the entire coding region and flanking intron regions were sequenced in 46 AMI/VF+ patients. In total, nine single nucleotide variants were identified of which four represented common single nucleotide polymorphisms (SNPs; 87G>A, 1673A>G, IVS16­6C>T and 5457T>A). Only five rare variants were identified, each in only one patient. Only two of the rare variants represented missense mutations (3578G>A and 4786T>A). The common SNPs and the missense mutations were also genotyped using polymerase chain reaction methods in 79 AMI/VF­ patients and 480 healthy controls. The SNPs did not demonstrate significant differences in allele and genotype frequencies between the study groups. The 3578G>A mutation was identified in one out of the 480 controls, whereas the 4786T>A mutation was not present in AMI/VF- patients and controls. In conclusion, the majority of AMI/VF+ patients demonstrated a wild type sequence or common SNPs in SCN5A. Only two out of 46 (4.3%) AMI/VF+ patients revealed mutations that may be involved in Nav1.5 dysfunction and VF. However, this requires further functional validation.


Assuntos
Infarto do Miocárdio/patologia , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Fibrilação Ventricular , Doença Aguda , Idoso , Éxons , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/genética , Pacientes , Polimorfismo de Nucleotídeo Único
9.
Int J Nurs Pract ; 20(4): 390-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24118372

RESUMO

This study aims to describe the health-promoting lifestyle behaviours of pregnant women. The study was carried out with pregnant women who applied to the polyclinics in different maternity and children hospitals located in Adana, Turkey, between 1 March and 30 May 2009. The data collection tools used in the study were (i) a questionnaire that was used to collect sociodemographic data from the participants and (ii) the Health Promoting Lifestyle Profile II (HPLP II). The results obtained from the study showed that total HPLP II scores were moderate; the highest scores were obtained on the spiritual growth dimension and the lowest scores on the physical activity dimension. Pregnant women with older age, those with a higher educational level, those with a better socioeconomic status and those living in a nuclear family were found to be more likely to have health-promoting lifestyles. Health promotion and healthy lifestyle need to be an integral part of health services provided for pregnant women. Midwives and nurses have prominent roles in encouraging pregnant women to engage in health-promoting behaviours.


Assuntos
Comportamentos Relacionados com a Saúde , Promoção da Saúde , Estilo de Vida , Adulto , Estudos Transversais , Demografia , Feminino , Humanos , Paridade , Gravidez , Inquéritos e Questionários , Turquia
11.
Clin Hemorheol Microcirc ; 54(1): 59-73, 2013 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-22750995

RESUMO

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 Tratamento
12.
World J Cardiol ; 4(6): 201-5, 2012 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-22761973

RESUMO

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.

13.
Heart Rhythm ; 9(8): 1295-300, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22406149

RESUMO

BACKGROUND: For years early repolarization (ER) has been considered as a benign electrocardiographic finding. However, recent reports show that ER is associated with a higher incidence of ventricular fibrillation (VF) and sudden cardiac death in patients without structural heart disease. Sporadic case studies have pointed out that ER might be related to an adverse outcome in patients with stable coronary artery disease. OBJECTIVE: To evaluate the incidence of ER in patients with acute myocardial infarction complicated by VF. METHODS: The study population consisted of 60 patients (80% men; mean age 61.8 ± 13.1 years) with acute myocardial infarction. Thirty consecutive patients (80% men; mean age 63.3 ± 12 years) admitted to our hospital had documented VF during myocardial infarction and were successfully resuscitated before hospital admission. A matched control group consisted of 30 patients (80% men; mean age 60.2 ± 14.2 years) with myocardial infarction without ventricular tachyarrhythmias. Twelve-lead electrocardiograms were analyzed for ER defined as J-point elevation ≥ 0.1 mV and "notching" and "slurring" of the terminal part of the QRS complex in at least 2 lateral or inferior leads. RESULTS: The ER pattern was observed in 18 of the 60 patients with acute myocardial infarction. Mean elevation of the J point was 0.151 ± 0.46 mV. Notching of the J wave was observed in 14 of the 18 patients and slurring in 4 of the 18 patients. ER was more common in patients with myocardial infarction complicated by VF than in patients with myocardial infarction without ventricular tachyarrhythmias (47% vs 13%; P = .005). There have been no statistical differences in the distribution of ER in the 12-lead electrocardiogram (inferior 39% vs lateral 33% vs inferolateral 28%; P >.05). CONCLUSION: Early repolarization pattern seems to be associated with ventricular tachyarrhythmias in the setting of acute myocardial infarction.


Assuntos
Eletrocardiografia , Sistema de Condução Cardíaco/fisiopatologia , Infarto do Miocárdio/complicações , Infarto do Miocárdio/fisiopatologia , Fibrilação Ventricular/complicações , Fibrilação Ventricular/fisiopatologia , Idoso , Estudos de Casos e Controles , Técnicas Eletrofisiológicas Cardíacas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Cardiol J ; 19(1): 20-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22298164

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/metabolismo
16.
Clin Appl Thromb Hemost ; 18(1): 87-91, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21733938

RESUMO

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 Cima
17.
Heart Vessels ; 27(2): 186-92, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21416113

RESUMO

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 Tempo
18.
Cardiovasc Pathol ; 21(2): 89-95, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21632263

RESUMO

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/metabolismo
20.
Cardiology ; 118(2): 107-15, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21546774

RESUMO

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 Umbilicais
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