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. 2021 Sep;35(9):107969.
doi: 10.1016/j.jdiacomp.2021.107969. Epub 2021 May 28.

Serum albumin modified by carbamoylation impairs macrophage cholesterol efflux in diabetic kidney disease

Aécio Lopes de Araújo Lira  1 , Monique de Fátima Mello Santana  1 , Raphael de Souza Pinto  1 , Carlos André Minanni  1 , Rodrigo Tallada Iborra  2 , Adriana Machado Saldiba de Lima  2 , Maria Lúcia Correa-Giannella  3 , Marisa Passarelli  4 , Márcia Silva Queiroz  5
Affiliations

Serum albumin modified by carbamoylation impairs macrophage cholesterol efflux in diabetic kidney disease

Aécio Lopes de Araújo Lira et al. J Diabetes Complications. 2021 Sep.

Abstract

Background 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 18h with albumin isolated from patients with eGFR<60mL/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 ≥60mL/min/1.73m2 per HDL2 (p=0.0001) and HDL3 (p<0.0001). Treatment for 48h showed that eGFR<15mL/min/1.73m2 had a lower percentage of 14C-cholesterol efflux mediated by HDL2 compared to control and other CKD groups (p=0.0274).

Conclusions: Albumins isolated from individuals with T2DM and eGFR<60mL/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.

Keywords: Advanced glycation; Carbamoylated albumin; Carbamoylation; Cholesterol efflux; Diabetic kidney disease; Reverse cholesterol transport.

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