RESUMO
BACKGROUND: Large observational studies have shown that small, dense LDL subfractions are related to atherosclerotic cardiovascular disease. This study assessed the effects of two highly effective lipid-lowering therapies in the atherogenic subclasses of lipoproteins in subjects with ST-segment elevation myocardial infarction (STEMI). METHODS: Patients of both sexes admitted with their first myocardial infarction and submitted to pharmacoinvasive strategy (N = 101) were included and randomized using a central computerized system to receive a daily dose of simvastatin 40 mg plus ezetimibe 10 mg or rosuvastatin 20 mg for 30 days. Intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) subfractions were analysed by polyacrylamide gel electrophoresis (Lipoprint System) on the first (D1) and 30th days (D30) of lipid-lowering therapy. Changes in LDL and IDL subfractions between D1 and D30 were compared between the lipid-lowering therapies (Mann-Whitney U test). RESULTS: The classic lipid profile was similar in both therapy arms at D1 and D30. At D30, the achievement of lipid goals was comparable between lipid-lowering therapies. Cholesterol content in atherogenic subclasses of LDL (p = 0.043) and IDL (p = 0.047) decreased more efficiently with simvastatin plus ezetimibe than with rosuvastatin. CONCLUSIONS: Lipid-lowering therapy with simvastatin plus ezetimibe was associated with a better pattern of lipoprotein subfractions than rosuvastatin monotherapy. This finding was noted despite similar effects in the classic lipid profile and may contribute to residual cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02428374, registered on 28/09/2014.
Assuntos
Lipoproteínas/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Idoso , Aterosclerose , Colesterol/sangue , LDL-Colesterol , Ezetimiba/administração & dosagem , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Lipídeos/sangue , Fígado/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Rosuvastatina Cálcica/administração & dosagem , Sinvastatina/administração & dosagem , Sinvastatina/sangueRESUMO
Monocytes circulate in the blood and migrate to inflammatory tissues, but their functions can be either detrimental or beneficial, depending on their phenotypes. In humans, classical monocytes are inflammatory cluster of differentiation (CD)14++CD16-CCR2++ cells originated from the bone marrow or spleen reservoirs and comprise ≥92% of monocytes. Intermediate monocytes (CD14++CD16+CCR2+) are involved in the production of anti-inflammatory cytokines [such as interleukin (IL)-10], reactive oxygen species (ROS), and proinflammatory mediators [such as tumor necrosis factor-α (TNF-α) and IL-1ß). Nonclassical monocytes (CD14+CD16++CCR2-) are patrolling cells involved in tissue repair and debris removal from the vasculature. Many studies in both humans and animals have shown the importance of monocyte chemoattractant protein-1 (MCP-1) and its receptor [chemokine receptor of MCP-1 (CCR2)] in pathologies, such as atherosclerosis and myocardial infarction (MI). This review presents the importance of these monocyte subsets in cardiovascular diseases (CVDs), and sheds light on new strategies for the blocking of the MCP-1/CCR2 axis as a therapeutic goal for treating vascular disorders.
Assuntos
Doenças Cardiovasculares/metabolismo , Quimiocina CCL2/metabolismo , Monócitos/metabolismo , Receptores CCR2/metabolismo , Animais , Anti-Inflamatórios/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/imunologia , Quimiocina CCL2/antagonistas & inibidores , Humanos , Ligantes , Monócitos/classificação , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Fenótipo , Receptores CCR2/antagonistas & inibidores , Transdução de SinaisRESUMO
The paper summarizes the difficulties to study the rare population of endothelial progenitor cells in clinical trials, based on the experience of our group in many publications in this area.
Assuntos
Células Progenitoras Endoteliais , Transplante de Células-Tronco/métodos , Ensaios Clínicos como Assunto , HumanosRESUMO
BACKGROUND: Increased numbers of endothelial (EMP) and platelet (PMP) microparticles have been related to cardiovascular risk factors and coronary artery disease. Little is known about the early effects of statins and clopidogrel on these new biomarkers of vascular homeostasis. The aim of the present study was to evaluate pharmacokinetic interactions between atorvastatin and clopidogrel and their effects, alone or combined, on EMP, PMP, and endothelial progenitor cells (EPC). METHODS AND RESULTS: A prospective open-label study enrolled subjects with stable coronary disease (n=26). Drugs were given daily for 3 weeks (atorvastatin 80 mg, visits 1-3; clopidogrel 75 mg, visits 2-4). Counts of EPC (CD34+/CD133+/KDR+), EMP (CD51+) and PMP (CD42+/CD31+), and pharmacokinetic parameters over 24h were assessed at each visit. Atorvastatin plasma concentrations were increased by concomitant therapy with clopidogrel (maximum serum concentration [C(max)], P=0.002; area under the clopidogrel or atorvastatin plasma concentration vs. time curve from 0 to the last detectable concentration [AUC(last)], P=0.03). After atorvastatin withdrawal there was an increase in clopidogrel plasma concentrations (C(max), P=0.009; AUC(last), P=0.039). PMP were inversely correlated with clopidogrel C(max) on visit 3 (rho=-0.57, P=0.006) and on visit 4 (rho=-0.54, P=0.01), and with clopidogrel AUC(last) on visit 3 (rho=-0.44, P=0.04), and on visit 4 (rho=-0.57, P=0.005). In addition, clopidogrel C(max) was correlated with EPC (CD133+/KDR+) on visit 4 (rho=0.48, P=0.025). No correlations of atorvastatin and MP or EPC were found. CONCLUSIONS: The balance between platelet MP release and EPC mobilization seems influenced by clopidogrel plasma levels, suggesting a protective mechanism on coronary artery disease.
Assuntos
Plaquetas/patologia , Doença da Artéria Coronariana/tratamento farmacológico , Células Endoteliais/patologia , Células-Tronco/patologia , Ticlopidina/análogos & derivados , Adulto , Idoso , Movimento Celular , Micropartículas Derivadas de Células/efeitos dos fármacos , Clopidogrel , Doença da Artéria Coronariana/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária , Substâncias Protetoras , Antagonistas do Receptor Purinérgico P2Y , Ticlopidina/sangue , Ticlopidina/farmacologiaRESUMO
FUNDAMENTO: Sabe-se que vários fatores interferem na sensibilidade do Eletrocardiograma (ECG) no diagnóstico da Hipertrofia Ventricular Esquerda (HVE), sendo o gênero e a massa cardíaca alguns dos principais. OBJETIVO: Avaliar a influência do sexo na sensibilidade de alguns dos critérios utilizados para a detecção de HVE, de acordo com a progressão do grau de hipertrofia ventricular. MÉTODOS: De acordo com o gênero e com o grau de HVE ao ecocardiograma, os pacientes foram divididos em três grupos: HVE leve, moderada e severa. Avaliou-se a sensibilidade do ECG para detectar HVE entre homens e mulheres, conforme o grau de HVE. RESULTADOS: Dos 874 pacientes, 265 eram homens (30,3 por cento) e 609, mulheres (69,7 por cento). Os critérios [(S + R) X QRS], Sokolow-Lyon, Romhilt-Estes, Perúgia e padrão strain mostraram alto poder discriminatório no diagnóstico de HVE entre homens e mulheres nos três grupos de HVE, com desempenho superior na população masculina e destaque para os escores [(S + R) X QRS] e Perúgia. CONCLUSÃO: A sensibilidade diagnóstica do ECG é maior com o aumento da massa cardíaca. O exame é mais sensível entre homens, destacando-se os escores [(S + R) X QRS] e Perúgia.
BACKGROUND: Several factors are known to interfere with electrocardiogram (ECG) sensitivity when diagnosing Left Ventricular Hypertrophy (LVH), with gender and cardiac mass being two of the most important ones OBJECTIVE: To evaluate the influence of gender on the sensitivity of some of the criteria used to detect LVH, according to the progression of ventricular hypertrophy degree. METHODS: According to gender and the degree of LVH at the echocardiogram, the patients were divided in three groups: mild, moderate and severe LVH. ECG sensitivity to detect LVH was assessed between men and women, according to the LVH degree. RESULTS: Of the 874 patients, 265 were males (30.3 percent) and 609, females (69.7 percent). The [(S + R) X QRS], Sokolow-Lyon, Romhilt-Estes, Perugia and strain criteria showed high discriminatory power in the diagnosis of LVH between men and women in the three groups with LVH, with a superior performance in the male population and highlighting the importance of the [(S + R) X QRS] and Perugia scores. Conclusion: The diagnostic sensitivity of the ECG increases with the cardiac mass. The examination is more sensitive in men, highlighting the importance of the [(S + R) X QRS] and Perugia scores. CONCLUSION: The diagnostic sensitivity of the ECG increases with the cardiac mass. The examination is more sensitive in men, highlighting the importance of the [(S + R) X QRS] and Perugia scores.
Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Eletrocardiografia , Hipertrofia Ventricular Esquerda/diagnóstico , Fatores Sexuais , Ecocardiografia , Ventrículos do Coração , Hipertrofia Ventricular Esquerda/fisiopatologia , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Several factors are known to interfere with electrocardiogram (ECG) sensitivity when diagnosing Left Ventricular Hypertrophy (LVH), with gender and cardiac mass being two of the most important ones OBJECTIVE: To evaluate the influence of gender on the sensitivity of some of the criteria used to detect LVH, according to the progression of ventricular hypertrophy degree. METHODS: According to gender and the degree of LVH at the echocardiogram, the patients were divided in three groups: mild, moderate and severe LVH. ECG sensitivity to detect LVH was assessed between men and women, according to the LVH degree. RESULTS: Of the 874 patients, 265 were males (30.3%) and 609, females (69.7%). The [(S + R) X QRS], Sokolow-Lyon, Romhilt-Estes, Perugia and strain criteria showed high discriminatory power in the diagnosis of LVH between men and women in the three groups with LVH, with a superior performance in the male population and highlighting the importance of the [(S + R) X QRS] and Perugia scores. Conclusion: The diagnostic sensitivity of the ECG increases with the cardiac mass. The examination is more sensitive in men, highlighting the importance of the [(S + R) X QRS] and Perugia scores. CONCLUSION: The diagnostic sensitivity of the ECG increases with the cardiac mass. The examination is more sensitive in men, highlighting the importance of the [(S + R) X QRS] and Perugia scores.
Assuntos
Eletrocardiografia , Hipertrofia Ventricular Esquerda/diagnóstico , Fatores Sexuais , Ecocardiografia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Cardiovascular events have been reported among HIV-infected patients following antiretroviral therapy. However, the role of HIV itself in determining vascular damage is less described. Chronic inflammatory state might impair some regulatory endothelium properties leading to its activation, apoptosis or erosion. OBJECTIVES: To evaluate the balance between endothelial progenitor cells and microparticles in HIV-infected antiretroviral drug-naive patients. DESIGN: A case-control study comparing HIV-infected patients (n = 35) with sex-matched and age-matched healthy controls (n = 33). METHODS: Endothelial progenitor cells populations expressing CD34, CD133 and KDR were quantified by flow cytometry. Endothelial-derived microparticles, expressing CD51, and platelet-derived microparticles, expressing CD31/CD42, were also measured. Endothelial function was estimated by flow-mediated dilation. RESULTS: Lower percentages of endothelial progenitor cells (CD34/KDR) were observed in HIV-infected individuals compared with controls (0.02 vs. 0.09%, P = 0.045). In addition, endothelial microparticles concentration was higher in HIV-infected individuals (1963 vs. 436 microparticles/µl platelet-poor plasma, P = 0.003), with similar number of platelet-derived microparticles among groups. Furthermore, flow-mediated dilation was lower among HIV-infected individuals compared with controls [mean (SEM): 10 (1) and 16% (2), respectively; P = 0.03]. CONCLUSION: Our findings suggest an imbalance between endothelial progenitor cells mobilization and endothelial apoptosis. The alteration in the turnover of endothelial cells may contribute to cardiovascular events in HIV-infected patients.
Assuntos
Micropartículas Derivadas de Células/metabolismo , Células Endoteliais/metabolismo , Endotélio Vascular/fisiopatologia , Infecções por HIV/fisiopatologia , Células-Tronco/metabolismo , Antígeno AC133 , Adulto , Antígenos CD/metabolismo , Antígenos CD34/metabolismo , Apoptose , Brasil , Estudos de Casos e Controles , Endotélio Vascular/metabolismo , Feminino , Citometria de Fluxo , Glicoproteínas/metabolismo , Infecções por HIV/metabolismo , Humanos , Integrina alfaV/metabolismo , Masculino , Pessoa de Meia-Idade , Peptídeos/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Estudos Prospectivos , Vasodilatação , Adulto JovemRESUMO
AIM: Based on evidence that ionizing radiation can ameliorate chronic and autoimmune diseases in patients and experimental animals, we investigated the effects of radiation on the induction and development of experimental atherogenesis. METHODS: Male New Zealand rabbits were divided into 5 groups and given an atherogenic diet for 90 days. Peritoneal and thoracic areas (9 Gy) were irradiated on the 1st and 45th days for groups 1 and 2, the 45th day for groups 3 and 4, and not at all for group 5. Prior to irradiation, the peritoneal cavity of animals from groups 1 and 3 was washed with buffered saline. Cells collected by peritoneal washing were reinfused into the peritoneal cavity of the same animal after irradiation. Animals from groups 2 and 4 were intraperitoneally injected with saline as a control. RESULTS: Despite similar lipid profiles among the experimental groups, the percentage of aortas covered by plaques was remarkably reduced (p<0.001) among animals submitted to irradiation (groups 2 and 4). These differences were completely abolished in irradiated animals reconstituted with their own peritoneal cells. CONCLUSIONS: These findings point to an important role of resident inflammatory peritoneal cells in experimental atherogenesis.
Assuntos
Líquido Ascítico/imunologia , Aterosclerose/etiologia , Inflamação/etiologia , Macrófagos Peritoneais/fisiologia , Monócitos/fisiologia , Cavidade Peritoneal/citologia , Animais , Citometria de Fluxo , Masculino , Cavidade Peritoneal/efeitos da radiação , Lavagem Peritoneal , Cavidade Pleural/citologia , Cavidade Pleural/efeitos da radiação , Coelhos , Radiação IonizanteRESUMO
BACKGROUND: Oxidized lipoproteins and antibodies anti-oxidized low-density lipoprotein (anti-oxLDL) have been detected in human plasma and in atherosclerotic lesions. However, the role of these autoantibodies in the maintenance of vascular health or in the pathogenesis of acute vascular insults remains unclear. We examined the relationship of human immunoglobulin G (IgG) anti-oxLDL antibodies with cardiovascular disease risk markers in stable subjects and in patients after an acute coronary syndrome (ACS). METHODS: Titers of human anti-oxLDL antibodies were measured in hypertensive subjects in primary prevention (n=94), without other risk factors, and in individuals after a recent ACS event who also had metabolic syndrome (n=116). Autoantibodies against copper ion oxidized LDL were measured by enzyme-linked-immunosorbent assay. RESULTS: Anti-oxLDL titers were higher in hypertensive patients and these subjects presented lower high sensitivity C-reactive protein (hs-CRP) than those with ACS (p<0.0001). We found significant correlations between anti-oxLDL and hs-CRP (r=-0.284), body mass index (r=-0.256), waist circumference (r=-0.368), apolipoprotein B (r=-0.191), glucose (r=-0.303), systolic blood pressure (r=0.319), diastolic blood pressure (r=0.167), high-density lipoprotein cholesterol (r=0.224) and apolipoprotein A1 (r=0.257) (p<0.02 for all). After multiple linear regression hs-CRP, fasting glucose and waist circumference remained independently and inversely associated with anti-oxLDL. CONCLUSIONS: Acute inflammatory and metabolic conditions decrease titers of human antibodies of IgG class against oxidized LDL, and that circulating anti-oxLDL antibodies could be associated with a protective role in atherosclerosis.
Assuntos
Autoanticorpos/sangue , Autoanticorpos/imunologia , Lipoproteínas LDL/imunologia , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/imunologia , Adulto , Idoso , Análise de Variância , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Feminino , Humanos , Hipertensão/sangue , Hipertensão/complicações , Hipertensão/imunologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: Patients with metabolic syndrome (MetS) are at high coronary risk and beta-cell dysfunction or insulin resistance might predict an additional risk for early cardiovascular events. OBJECTIVE: This study aimed to evaluate early glucometabolic alterations in patients with MetS, but without previously known type 2 diabetes, after acute coronary syndrome. METHODS: A total of 114 patients were submitted to an oral glucose tolerance test (OGTT) 1-3 days after hospital discharge due to myocardial infarction or unstable angina. Based on the OGTT, we defined three groups of patients: normal glucose tolerance (NGT; n=26), impaired glucose tolerance (IGT; n=39), or diabetes (DM; n=49). The homeostasis model assessment (HOMA-IR) was used to measure insulin resistance; beta-cell responsiveness was assessed by the insulinogenic index at 30 min (DeltaI30/DeltaG30). RESULTS: Based on the HOMA-IR, patients with DM were more insulin-resistant than those with NGT or IGT (p<0.001). According to the insulinogenic index, the beta-cell responsiveness was also impaired in subjects with DM (p<0.001 vs NGT or IGT). CONCLUSION: High rates of glucometabolic alterations were found after acute coronary syndrome in patients with MetS. As these abnormalities markedly increase the risk for adverse outcomes, early OGTT among MetS patients might be used to identify those at the highest coronary risk.