MONIQUE DE FATIMA MELLO SANTANA
Projetos de Pesquisa
Unidades Organizacionais
LIM/10 - Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina
2 resultados
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- Serum albumin modified by carbamoylation impairs macrophage cholesterol efflux in diabetic kidney disease(2021) LIRA, Aecio Lopes de Araujo; SANTANA, Monique de Fatima Mello; PINTO, Raphael de Souza; MINANNI, Carlos Andre; IBORRA, Rodrigo Tallada; LIMA, Adriana Machado Saldiba de; CORREA-GIANNELLA, Maria Lucia; PASSARELLI, Marisa; QUEIROZ, Marcia SilvaBackground and aims: Abnormalities in lipid metabolism, accumulation of uremic toxins and advanced glycation end products may contribute to worsening atherosclerosis. This study characterized the glycation and carbamoylation profile of serum albumin isolated from individuals with diabetic kidney disease and its influence on cholesterol efflux. Material and methods: 49 patients with type 2 diabetes (T2DM) and different eGFR evaluated glycation and carbamoylation profile by measurement of carboxymethyl lysine (CML) and carbamoylated proteins (CBL) in plasma by ELISA, homocitrulline (HCit) in plasma by colorimetry. In the isolated albumins, we quantified CBL (ELISA) and total AGE and pentosidine by fluorescence. Macrophages were treated with albumin isolated, and 14C-Cholesterol efflux mediated by HDL2 or HDL3 was measured. Kruskal-Wallis test, Jonckheere-Terpstra test and Brunner's posttest were used for comparisons among groups. Results: Determination of CML, HCit, CBL in plasma, as total AGE and pentosidine in albumins, did not differ between groups; however, CBL in the isolated albumins was higher in the more advanced stages of CKD (p = 0.0414). There was reduction in the 14C-cholesterol efflux after treatment for 18 h with albumin isolated from patients with eGFR<60 mL/min/1.73m2 compared with control group mediated by HDL2 (p = 0.0288) and HDL3 (p < 0.0001), as well as when compared with eGFR >= 60 mL/min/1.73m2 per HDL2 (p = 0.0001) and HDL3 (p < 0.0001). Treatment for 48 h showed that eGFR<15 mL/min/1.73m2 had a lower percentage of 14Ccholesterol efflux mediated by HDL2 compared to control and other CKD groups (p = 0.0274). Conclusions: Albumins isolated from individuals with T2DM and eGFR<60 mL/min/1.73m2 suffer greater carbamoylation, and they impair the cholesterol efflux mediated by HDL2 and HDL3. In turn, this could promote lipids accumulation in macrophages and disorders in reverse cholesterol transport.
- Persistent Effect of Advanced Glycated Albumin Driving Inflammation and Disturbances in Cholesterol Efflux in Macrophages(2021) MINANNI, Carlos Andre; MACHADO-LIMA, Adriana; IBORRA, Rodrigo Tallada; OKUDA, Ligia Shimabukuro; PINTO, Raphael de Souza; SANTANA, Monique de Fatima Mello; LIRA, Aecio Lopes de Araujo; NAKANDAKARE, Edna Regina; CORREA-GIANNELLA, Maria Lucia Cardillo; PASSARELLI, MarisaAdvanced 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.