Microparticles: potential new contributors to the pathogenesis of systemic sclerosis?

Abstract Background Microparticles (MPs) are membrane-derived vesicles released from cells undergoing activation or apoptosis with diverse proinflammatory and prothrombotic activities, that have been implicated in the pathogenesis of systemic sclerosis (SSc). We aimed to evaluate the plasma levels of platelet-derived microparticles (PMPs), endothelial cell-derived microparticles (EMPs), and monocyte-derived microparticles (MMPs) in SSc patients, and the association between MPs and the clinical features of SSc. Methods In this cross-sectional study, 70 patients with SSc and 35 age- and sex-matched healthy controls were evaluated. Clinical and nailfold capillaroscopy (NFC) data were obtained from all patients. Plasma levels of PMPs (CD42+/31+), EMPs (CD105+), and MMPs (CD14+) were quantified by flow cytometry. Results Patients were mainly females (90%), with a mean age of 48.9 years old. PMP, EMP, and MMP levels were significantly increased in SSc patients compared to controls (79.2% ± 17.3% vs. 71.0% ± 19.8%, p = 0.033; 43.5% ± 8.7% vs. 37.8% ± 10.4%, p = 0.004; and 3.5% ± 1.3% vs. 1.1% ± 0.5%, p < 0.0001, respectively). PMP levels were significantly higher in patients with positive anti-topoisomerase-I antibodies (p = 0.030) and in patients with a disease duration > 3 years (p = 0.038). EMP levels were lower in patients with a higher modified Rodnan skin score (p = 0.015), and in those with an avascular score > 1.5 in NFC (p = 0.042). Conclusion The increased levels of PMPs, EMPs and MMPs in scleroderma patients might indicate a possible role for these agents in the pathogenesis of this challenging disease.

Monocytes presenting a pro-inflammatory profile persist in patients submitted to a long-term pharmacological treatment after acute myocardial infarction.

Introduction: Although it is broadly known that monocyte recruitment is involved in atherosclerosis development and that, in accordance with the microenvironment, these cells can be modulated into three well-known subpopulations: Classical (CD14++CD16-), intermediate (CD14++CD16+), and non-classical (CD14+CD16++), the effects of treatment with different pharmacological strategies (based on lipid-lowering and antiplatelets) after acute myocardial infarction upon the monocytes modulation and the role of the chemokine receptors CCR2, CCR5 and CX3CR1 in this context, are poorly understood. Methods: In this study, patients [n = 148, both men (n = 105, 71%) and women (n = 43, 29%)] submitted to treatment with a 2×2 factorial design, in which they received rosuvastatin 20 mg or simvastatin 40 mg plus ezetimibe 10 mg, as well as ticagrelor 90 mg or clopidogrel 75 mg were enrolled. Monocyte subsets were analyzed by flow cytometry at baseline (BL), and after one (1-M) and 6 months (6-M) of treatment. Results: Firstly, our results showed that, regardless of the treatment received, higher percentages of classical monocytes and lower of non-classical monocytes were found at the 6-M time point than BL values, whilst the percentage of intermediate monocytes was higher in all time points assessed than the other subsets. There were reductions in the CCR2 expression by non-classical and intermediate monocytes, without differences for the classical subtype. Concerning the CCR5 expression, there were reductions in the three monocyte subtypes, whereas the CX3CR1 expression increased both in intermediate and classical monocytes, without differences for non-classical monocytes. In relation to the treatment received, a higher percentage of intermediate monocytes at the 6-M time point than the values BL was observed in the group treated with simvastatin + ezetimibe + clopidogrel. No significant differences were found concerning non-classical, intermediate, and classical monocytes, for CCR2, CCR5, and CX3CR1 in the four treatment arms. Conclusion: Taken together, our results demonstrated that even under lipid-lowering and antiplatelet therapy for 6 months, the inflammatory phenotype of monocytes still persisted in the patients enrolled in this study.

Subpopulações de linfócitos B e parâmetros imunes na evolução do infarto agudo do miocárdio com supradesnivelamento do segmento ST / B lymphocyte subpopulations and immune parameters in the evolution of ST-segment elevation acute myocardial infarction

INTRODUÇÃO: A reperfusão precoce é recomendada universalmente para tratamento de pacientes com infarto agudo do miocárdico com supradesnivelamento do segmento ST (IAMCST). Entretanto, apesar de rápida reperfusão com angioplastia primária ou química, alguns pacientes ainda apresentam grandes massas de fibrose miocárdica e, portanto, queda significativa da função ventricular. OBJETIVO: avaliar o papel da resposta inflamatória mediada pelos linfócitos B na massa de infarto e na função ventricular após IAMCST. Métodos: amostras de sangue venoso foram coletadas no primeiro (D1) e trigésimo dia (D30) de pacientes com IAMCST(n=120), submetidos a estratégia fármacoinvasiva.A quantificação dos linfócitos B e T foi determinada por citometria de fluxo. A secreção espontânea de imunoglobulina M (IgM) pelos linfócitos B1, foi quantificada por ELISPOT. IgM total e níveis de interleucinas (IL) plasmáticas foram determinadas por ELISA. A massa de infarto e a fração de ejeção do ventrículo esquerdo (FEVE) foram estimadas por ressonância nuclear magnética cardíaca em D30. RESULTADOS: houve queda no número absoluto (cels/mL) das subpopulações de linfócitos B1 e B2 em D30...(AU)

Análise crítica dos estudos que mudaram a prática clínica recente: dislipidemias / Critical analysis of studies that changed recent clinical practice: dyslipidemias

Os eventos isquêmicos continuam a ocorrer em pacientes com fatores de risco mal controlados, como os que têm concentrações elevadas de LDL-colesterol ou de triglicérides, nos que têm diabetes e doença aterosclerótica multivascular, a despeito do tratamento com estatinas. Além dos eventos iniciais, esses pacientes têm risco substancial de eventos recorrentes, possivelmente fatais. A avaliação dos eventos recorrentes traz a perspectiva da carga total de eventos ateroscleróticos a que esses pacientes estão expostos e não apenas dos primeiros eventos. Dois estudos com novas terapêuticas hipolipemiantes abordaram a redução de eventos cardiovasculares e também de eventos totais, de um primeiro evento e de eventos subsequentes. O evolocumabe, um inibidor da pró-proteína convertase subtilisina/quexina tipo 9 e o icosapenta etil, formulação altamente purificada de ácido graxo ômega 3 demonstraram reduções dos eventos cardiovasculares primários e secundários chave, bem como dos eventos totais, dos primeiros eventos e dos eventos subsequentes em pacientes de alto risco e risco muito alto que usam estatinas, mas com um risco elevado de novos eventos cardiovasculares. Pelos benefícios demonstrados, essas estratégias terapêuticas poderão ser incorporadas à prática clínica, desde que avaliadas num contexto de risco e benefício, e com um custo-efetividade aceitável

Ischemic events continue to occur in patients with poorly controlled risk factors, such as those with high concentrations of LDL-cholesterol or triglycerides and those with diabetes and multivascular artherosclerotic disease, in spite of treatment with statins. These patients are at risk not only for the first, but also for recurrent ischemic events, which can be fatal. The evaluation of recurrent events brings a perspective of the total burden of artherosclerotic events to which the patient is exposed and not only of the first one. Two studies using new lipid-lowering therapies addressed the reduction of cardiovascular events and also of total events, of a first event, and of subsequent events. Evolocumab, a proprotein convertase subutilisin kexin type 9 inhibitor, and icosapent ethyl, a highly purified formulation of omega-3 fatty acid, demonstrated reductions in key primary and secondary cardiovascular events, as well as in total events, first events and subsequent events in high and very high risk patients taking statins, but with a high risk of new cardiovascular events. Based on the benefits observed, these therapeutic strategies can be incorporated into clinical practice, provided they are evaluated within a risk benefit context, with an acceptable cost-effectiveness ratio