Níveis de células progenitoras endoteliais e micropartículas circulantes em pacientes de alto risco recebendo tratamento hipolipemiante
Data
2014-08-31
Autores
Lins, Livia Campos do Amaral Silva 
Orientadores
Izar, Maria Cristina de Oliveira
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Objetivo: A inflamação e a doença arterial coronariana modulam o turnover de células endoteliais e podem prever desfechos. Nosso estudo teve por objetivo avaliar os efeitos de terapias hipolipemiantes em células progenitoras endoteliais (CPE), micropartículas endoteliais (MPE) e plaquetárias (MPP) em pacientes de alto-risco com níveis elevados de Proteína C-reativa (PCR). Métodos e Resultados: Foram selecionados 63 pacientes com doença arterial coronariana (CAD) ou seus equivalentes de risco, sob tratamento com estatinas. Após run-in de 4 semanas, com atorvastatina 10 mg, os pacientes que possuíam níveis de colesterol LDL(LDL-C) <100 mg/dL e PCR >2.0 mg/L foram randomizados para mais 4 semanas de tratamento com atorvastatina 40mg, ezetimibaa 10mg ou a combinação de atorvastatina 40mg / ezetimiba 10mg. O estudo foi randomizado, aberto, com os braços paralelos e com desfechos cegos. CPE (CD34+/CD133+/KDR+), MPE (CD51+) e MPP (CD42+/CD31+) foram quantificadas por citometria de fluxo no período basal e ao final do estudo. Os grupos atorvastatina 40mg e atorvastatina 40mg / ezetimiba 10mg reduziram o LDL-C (P<0.001 vs. basal, teste-T pareado). A terapia de associação reduziu os níveis de PCR ultra-sensível (PCR-us), enquanto o grupo ezetimiba 10 mg aumentou o LDL-C (P<0.001 vs. basal, teste-T pareado) e não modificou os níveis de PCR-us. Redução nas CPE CD34+/KDR foi observada após terapia com ezetimiba isolada (P=0.011 vs. basal, teste de Wilcoxon) ou combinada com atorvastatina (P=0.016 vs. basal, teste de Wilcoxon). A ezetimiba também elevou os níveis de MPE CD51+ (P=0.017 vs. basal, teste de Wilcoxon). Nenhuma relação com o LDL-C e a PCR foi observada para estes marcadores. Conclusões: Estes resultados contribuem para melhor compreensão da ligação entre inflamação e homeostase vascular e destacar o benefício das estatinas na diminuição da inflamação e na prevenção de liberação de micropartículas, um efeito não observado com a ezetimiba.
Aims: Coronary artery disease and inflammation modulate endothelial cells turnover and can predict outcomes. Our study aimed at evaluating the effects of lipidmodifying therapies on endothelial progenitor cells (EPC), endothelial (EMP) and platelet microparticles (PMP) in high-risk subjects with elevated C-reactive protein (CRP) levels. Methods and Results: Sixty-three individuals with coronary heart disease (CHD) or CHD risk equivalent on stable statin therapy were selected. After a 4-week run-in period with atorvastatin 10mg, those attaining LDL-cholesterol <100 mg/dL and CRP levels >2.0 mg/L were randomized to another four-week treatment period with atorvastatin 40mg, ezetimibe 10mg or the combination of atorvastatin 40mg / ezetimibe 10mg. The study was randomized, open label, with parallel arms and blinded endpoints. EPC (CD34+/CD133+/KDR+), EMP (CD51+) and PMP (CD42+/CD31+) were quantified by flow-citometry at baseline and end of study. Atorvastatin 40mg and atorvastatin 40mg / ezetimibe 10mg reduced LDL-cholesterol (P<0.001, paired t-test, vs. baseline). Combined therapy reduced hs-CRP, whereas ezetimibe increased LDL-cholesterol (P<0.001 vs. baseline, paired T-test); and did not modify CRP. Reduction in CD34+/KDR+ EPC was observed after ezetimibe alone (P=0.011 vs. baseline, Wilcoxon test) or combined with atorvastatin (P=0.016 vs. baseline, Wilcoxon test), whereas ezetimibe also increased CD51+ EMP (P=0.017 vs. baseline, Wilcoxon test). No correlations with on-treatment LDL cholesterol or CRP levels were observed for these markers. Conclusions: These results contribute to better understand the link between inflammation and vascular homeostasis and highlight the broader benefit of statins decreasing inflammation and preventing microparticles release, an effect not observed with ezetimibe.
Aims: Coronary artery disease and inflammation modulate endothelial cells turnover and can predict outcomes. Our study aimed at evaluating the effects of lipidmodifying therapies on endothelial progenitor cells (EPC), endothelial (EMP) and platelet microparticles (PMP) in high-risk subjects with elevated C-reactive protein (CRP) levels. Methods and Results: Sixty-three individuals with coronary heart disease (CHD) or CHD risk equivalent on stable statin therapy were selected. After a 4-week run-in period with atorvastatin 10mg, those attaining LDL-cholesterol <100 mg/dL and CRP levels >2.0 mg/L were randomized to another four-week treatment period with atorvastatin 40mg, ezetimibe 10mg or the combination of atorvastatin 40mg / ezetimibe 10mg. The study was randomized, open label, with parallel arms and blinded endpoints. EPC (CD34+/CD133+/KDR+), EMP (CD51+) and PMP (CD42+/CD31+) were quantified by flow-citometry at baseline and end of study. Atorvastatin 40mg and atorvastatin 40mg / ezetimibe 10mg reduced LDL-cholesterol (P<0.001, paired t-test, vs. baseline). Combined therapy reduced hs-CRP, whereas ezetimibe increased LDL-cholesterol (P<0.001 vs. baseline, paired T-test); and did not modify CRP. Reduction in CD34+/KDR+ EPC was observed after ezetimibe alone (P=0.011 vs. baseline, Wilcoxon test) or combined with atorvastatin (P=0.016 vs. baseline, Wilcoxon test), whereas ezetimibe also increased CD51+ EMP (P=0.017 vs. baseline, Wilcoxon test). No correlations with on-treatment LDL cholesterol or CRP levels were observed for these markers. Conclusions: These results contribute to better understand the link between inflammation and vascular homeostasis and highlight the broader benefit of statins decreasing inflammation and preventing microparticles release, an effect not observed with ezetimibe.
Descrição
Citação
LINS, Livia Campos do Amaral Silva. Níveis de células progenitoras endoteliais e micropartículas circulantes em pacientes de alto risco recebendo tratamento hipolipemiante. 2012. Dissertação (Mestrado) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2012.