Advanced glycated albumin impairs HDL anti-inflammatory activity and primes macrophages for inflammatory response that reduces reverse cholesterol transport

Autor(es)

Okuda, Ligia S. ^[1] ; Castilho, Gabriela ^[1] ; Rocco, Debora D. F. M. ^[1] ; Nakandakare, Edna R. ^[1] ; Catanozi, Sergio ^[1] ; Passarelli, Marisa ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Lipids Lab LIM 10, BR-01246000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS; v. 1821, n. 12, p. 1485-1492, DEC 2012.
• Citações Web of Science: 18

Resumo

Objective: We investigated the effect of advanced glycated albumin (AGE-albumin) on macrophage sensitivity to inflammation elicited by S100B calgranulin and lipopolysaccharide (LPS) and the mechanism by which HDL modulates this response. We also measured the influence of the culture medium, isolated from macrophages treated with AGE-albumin, on reverse cholesterol transport (RCT). Methods and results: Macrophages were incubated with control (C) or AGE-albumin in the presence or absence of HDL, followed by incubations with S100B or LPS. Also, culture medium obtained from cells treated with C- or AGE-albumin, following S100B or LPS stimulation was utilized to treat naive macrophages in order to evaluate cholesterol efflux and the expression of HDL receptors. In comparison with C-albumin, AGE-albumin, promoted a greater secretion of cytokines after stimulation with S100B or LPS. A greater amount of cytokines was also produced by macrophages treated with AGE-albumin even in the presence of HDL Cytokine-enriched medium, drawn from incubations with AGE-albumin and S100B or LPS impaired the cholesterol efflux mediated by apoA-I (23% and 37%, respectively), HDL2 (43% and 47%, respectively) and HDL3 (20% and 8.5%, respectively) and reduced ABCA-1 protein level (16% and 26%, respectively). Conclusions: AGE-albumin primes macrophages for an inflammatory response impairing the RCT. Moreover, AGE-albumin abrogates the anti-inflammatory role of HDL, which may aggravate the development of atherosclerosis in DM. (C) 2012 Elsevier BM. All rights reserved. (AU)

• Processo FAPESP: 09/53869-9 - Influência da modificação da albumina no diabete melito sobre a expressão diferencial de genes e o fluxo de lípides em macrófagos
• Beneficiário: Marisa Passarelli
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 06/52702-5 - Influência do treinamento físico aeróbio sobre o transporte reverso do colesterol em camundongos C57Bl/6J selvagens e trangênicos para CETP humana
• Beneficiário: Débora Dias Ferraretto Moura Rocco
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 10/50108-4 - Glicoxidação intracelular e estresse do retículo endoplasmático: efeito potenciais sobre os transportadores ABCA-1 e sobre o fluxo de lípides em macrófagos
• Beneficiário: Gabriela Castilho
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 10/50147-0 - Albumina modificada por glicação avançada sensibiliza macrófagos a inflamação prejudicando o transporte reverso de colesterol e a atividade anti-inflamatória da HDL
• Beneficiário: Ligia Shimabukuro Okuda
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto