Avaliação dos níveis plasmáticos de micropartículas e da efetividade do ácido acetilsalicílico sobre marcadores de disfunção vascular em pacientes com esclerose sistêmica
Data
2022-12-06
Autores
Oliveira, Sandra Maximiano 
Orientadores
Kayser, Cristiane
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: A esclerose sistêmica (ES) é uma doença reumática autoimune cujo evento patogênico primário é a injúria vascular à microcirculação. Objetivo: Neste estudo, pretendemos avaliar a eficácia do ácido acetilsalicílico (AAS) sobre marcadores de dano vascular (tromboxano B2 [TX], fator de von Willebrand [fvW] e micropartículas derivadas de plaquetas [MPP], células endoteliais [MPE], e monócitos [MPM]) em pacientes com ES. Objetivamos ainda comparar os níveis plasmáticos de micropartículas (MPs) entre pacientes com ES e controles saudáveis. Métodos: Realizamos ensaio clínico randomizado, duplo-cego, placebo-controlado, no qual os pacientes com ES foram alocados para receber AAS 100 mg/dia (n=35) ou placebo (n=35) durante quatro semanas. Os níveis plasmáticos de MPP (FITC-CD42+/PE-CD31+), MPE (APC-CD105+) e MPM (FITC-CD14+) foram dosados nos tempos basal (T0) e final (T1) pelo método de citometria de fluxo. Os níveis plasmáticos de TX e fvW foram dosados por ELISA nos tempos T0 e T1. O desfecho primário estipulado foi a mudança nos níveis de TX entre T0 e T1. Um grupo controle composto por 35 indivíduos saudáveis, pareados para sexo e idade, também foi incluído para comparação dos níveis de MPs entre estes e os pacientes com ES. Resultados: Foram avaliados 70 pacientes com ES (idade média de 48,9 anos, 90% sexo feminino), com tempo médio de duração de doença de 6,4 anos. Após quatro semanas de intervenção, houve redução significativa nos níveis plasmáticos de TX (13,0 ± 7,8 ng/ml no T0, versus 10,3 ± 5,1 ng/ml no T1) no grupo AAS, sem diferença no grupo placebo (15,5 ± 6,8 ng/ml no T0, versus 13,9 ± 6,8 ng/ml no T1) (p = 0.044). Os níveis plasmáticos de MPs foram significativamente maiores em pacientes com ES comparados a controles saudáveis (média ± DP): 79,2% ± 17,3% versus 71,0% ± 19,8% para MPP (p = 0,033); 43,5% ± 8,7% versus 37,8% ± 10,4% para MPE (p = 0,004); e 3,5% ± 1,3% versus 1,1% ± 0,5% para MPM (p < 0,0001). Efeitos adversos graves foram observados em três pacientes, mas não foram relacionados ao estudo. Conclusão: O uso de AAS 100 mg/dia por quatro semanas foi seguro e eficaz em reduzir os níveis plasmáticos de tromboxano B2 em pacientes com ES. Adicionalmente, micropartículas derivadas de plaquetas, células endoteliais e monócitos estão elevadas em doentes com ES, indicando um possível papel desses agentes nos mecanismos patogênicos da doença.
Background: Systemic sclerosis (SSc) is an autoimmune rheumatic disease whose primary pathogenic event is vascular injury to the microcirculation. Objective: In this study, we intend to evaluate the effectiveness of acetylsalicylic acid (ASA) on markers of vascular damage (thromboxane B2, von Willebrand factor [vWF], and platelet-derived microparticles [PMP], endothelial cells-derived microparticles [EMP], monocytes-derived microparticles [MMP]) in SSc patients. We also aimed to compare the serum levels of microparticles (MPs) between patients with SSc and healthy controls. Methods: We performed a randomized, double-blind, placebo-controlled clinical trial, in which patients with SSc were allocated to receive ASA 100 mg/day (n=35) or placebo (n=35) for four weeks. Plasma levels of PMP (FITC-CD42+/PE-CD31+), EMP (APC-CD105+) and MMP (FITC-CD14+) were measured at baseline (T0) and final (T1) times using flow cytometry. Plasma levels of TX and vWF were measured by ELISA at T0 and T1. The primary outcome was the change in the levels of TX between T0 and T1. A control group composed of 35 healthy individuals, sex and age-matched, was also included for comparison of MPs levels between them and the patients with SSc. Results: We evaluated 70 patients with SSc (mean age 48.9 years, 90% female), with a mean disease duration of 6.4 years. After four weeks of intervention, there was a significant reduction in the plasma levels of TX (13.0 ± 7.8 ng/ml at T0, versus 10.3 ± 5.1 ng/ml at T1) in the ASA group, with no difference in the placebo group (15.5 ± 6.8 ng/ml at T0, versus 13.9 ± 6.8 ng/ml at T1) (p = 0.044). Plasma levels of MPs were significantly increased in patients with SSc compared to healthy controls (mean ± SD): 79.2% ± 17.3% versus 71.0% ± 19.8% for PMP (p = 0.033); 43.5% ± 8.7% versus 37.8% ± 10.4% for EMP (p = 0.004); and 3.5% ± 1.3% versus 1.1% ± 0.5% for MMP (p < 0.0001). Serious adverse events were reported in three patients, but not related to the study. Conclusions: The use of ASA 100 mg/ day for four weeks was safe and effective in reducing plasmatic levels of thromboxane B2 in patients with SSc. Additionally, microparticles derived from platelets, endothelial cells and monocytes are elevated in patients with SSc, indicating a possible role of these agents in the pathogenic mechanisms of the disease.
Background: Systemic sclerosis (SSc) is an autoimmune rheumatic disease whose primary pathogenic event is vascular injury to the microcirculation. Objective: In this study, we intend to evaluate the effectiveness of acetylsalicylic acid (ASA) on markers of vascular damage (thromboxane B2, von Willebrand factor [vWF], and platelet-derived microparticles [PMP], endothelial cells-derived microparticles [EMP], monocytes-derived microparticles [MMP]) in SSc patients. We also aimed to compare the serum levels of microparticles (MPs) between patients with SSc and healthy controls. Methods: We performed a randomized, double-blind, placebo-controlled clinical trial, in which patients with SSc were allocated to receive ASA 100 mg/day (n=35) or placebo (n=35) for four weeks. Plasma levels of PMP (FITC-CD42+/PE-CD31+), EMP (APC-CD105+) and MMP (FITC-CD14+) were measured at baseline (T0) and final (T1) times using flow cytometry. Plasma levels of TX and vWF were measured by ELISA at T0 and T1. The primary outcome was the change in the levels of TX between T0 and T1. A control group composed of 35 healthy individuals, sex and age-matched, was also included for comparison of MPs levels between them and the patients with SSc. Results: We evaluated 70 patients with SSc (mean age 48.9 years, 90% female), with a mean disease duration of 6.4 years. After four weeks of intervention, there was a significant reduction in the plasma levels of TX (13.0 ± 7.8 ng/ml at T0, versus 10.3 ± 5.1 ng/ml at T1) in the ASA group, with no difference in the placebo group (15.5 ± 6.8 ng/ml at T0, versus 13.9 ± 6.8 ng/ml at T1) (p = 0.044). Plasma levels of MPs were significantly increased in patients with SSc compared to healthy controls (mean ± SD): 79.2% ± 17.3% versus 71.0% ± 19.8% for PMP (p = 0.033); 43.5% ± 8.7% versus 37.8% ± 10.4% for EMP (p = 0.004); and 3.5% ± 1.3% versus 1.1% ± 0.5% for MMP (p < 0.0001). Serious adverse events were reported in three patients, but not related to the study. Conclusions: The use of ASA 100 mg/ day for four weeks was safe and effective in reducing plasmatic levels of thromboxane B2 in patients with SSc. Additionally, microparticles derived from platelets, endothelial cells and monocytes are elevated in patients with SSc, indicating a possible role of these agents in the pathogenic mechanisms of the disease.