Persistent Effect of Advanced Glycated Albumin Driving Inflammation and Disturbances in Cholesterol Efflux in Macrophages

Author(s)

Minanni, Carlos Andre ^{[1, 2]} ; Machado-Lima, Adriana ^{[3, 1]} ; Iborra, Rodrigo Tallada ^{[1, 4]} ; Okuda, Ligia Shimabukuro ^[1] ; Pinto, Raphael de Souza ^[1] ; Mello Santana, Monique de Fatima ^[1] ; de Araujo Lira, Aecio Lopes ^[1] ; Nakandakare, Edna Regina ^[1] ; Cardillo Correa-Giannella, Maria Lucia ^[5] ; Passarelli, Marisa ^{[6, 1]}

Affiliation

^[1] Univ Sao Paulo, Lab Lipides LIM 10, Hosp Clin HCFMUSP, Fac Med, BR-01246000 Sao Paulo - Brazil

^[2] Hosp Israelita Albert Einstein HIAE, BR-05652900 Sao Paulo - Brazil

^[3] Univ Sao Judas Tadeu, Programa Posgrad Ciencias Envelhecimento, BR-03166000 Sao Paulo - Brazil

^[4] Univ Sao Judas Tadeu, Programa Posgrad Educ Fis, BR-03166000 Sao Paulo - Brazil

^[5] Univ Sao Paulo, Lab Carboidratos & Radioimunoensaio LIM 18, Hosp Clin HCFMUSP, Fac Med, BR-01246000 Sao Paulo - Brazil

^[6] Univ Nove de Julho, Programa Posgrad Med, BR-01525000 Sao Paulo - Brazil

• Document type: Journal article
• Source: NUTRIENTS; v. 13, n. 10 OCT 2021.
• Web of Science Citations: 1

Abstract

Advanced glycated albumin (AGE-albumin) impairs cholesterol efflux and contributes to inflammation in macrophages. The current study evaluated: (1) the persistence of the deleterious effect of AGE-albumin in cholesterol efflux and in inflammation, and (2) how metabolic control in diabetes mellitus (DM) contributes to attenuate the deleterious role of AGE-albumin in macrophage cholesterol homeostasis. Methods: AGE-albumin was produced in vitro or isolated from uncontrolled DM subjects' serum before (bGC) and after improved glycemic control (aGC). Albumin samples were incubated with bone marrow-derived macrophages and C-14-cholesterol efflux or LPS- induced cytokine secretion were determined immediately, or after cell resting in culture media alone. The ABCA-1 degradation rate was determined after cell incubation with cycloheximide, and ABCA1 protein level by immunoblot. Oil Red O staining was used to assess intracellular lipid accumulation. Results: A persistent effect of AGE-albumin was observed in macrophages in terms of the secretion of inflammatory cytokines and reduced cholesterol efflux. HDL-mediated C-14-cholesterol efflux was at least two times higher in macrophages treated with aCG-albumin as compared to bGC-albumin, and intracellular lipid content was significantly reduced in aGC-albumin-treated cells. As compared to bGC-albumin, the ABCA-1 protein content in whole cell bulk was 94% higher in aCG-albumin. A 20% increased ABCA-1 decay rate was observed in macrophages treated with albumin from poorly controlled DM. AGE-albumin has a persistent deleterious effect on macrophage lipid homeostasis and inflammation. The reduction of AGEs in albumin ameliorates cholesterol efflux.</p> (AU)

• FAPESP's process: 17/18545-4 - HDL proteomics and functionality in diabetes mellitus chronic kidney disease: association with advanced glycation end products
• Grantee: Monique de Fatima Mello Santana
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 12/19112-0 - Involvement of the RAGE/AGE axis in macrophage lipid accumulation induced by human advanced glycated albumin - contribution of glycemic control in diabetes mellitus.
• Grantee: Adriana Machado Saldiba de Lima
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 16/15603-0 - Unraveling mechanisms of glycemic control and chronic complications of Diabetes mellitus: contributions to human health
• Grantee: Ubiratan Fabres Machado
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/12088-7 - Glycemic control and the removal of macrophage cholesterol by ABCA-1: role of modified albumin by advanced glycation
• Grantee: Rodrigo Tallada Iborra
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/00172-0 - Advanced glycation products, endoplasmic reticulum stress and the modulation of the reverse cholesterol transport in human arteries with different levels Atherosclerotic lesion
• Grantee: Raphael de Souza Pinto
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/21072-5 - Influence of the glycemic control and nephropathy stage on the reverse cholesterol transport in Diabetes mellitus: role of metabolic memory induced by advanced glycated albumin
• Grantee: Marisa Passarelli
• Support Opportunities: Regular Research Grants