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

Author(s)

Lira, Aecio Lopes de Araujo ^[1] ; Santana, Monique de Fatima Mello ^[1] ; Pinto, Raphael de Souza ^[1] ; Minanni, Carlos Andre ^[1] ; Iborra, Rodrigo Tallada ^{[2, 1]} ; Lima, Adriana Machado Saldiba de ^{[2, 1]} ; Correa-Giannella, Maria Lucia ^{[3, 4]} ; Passarelli, Marisa ^{[1, 3]} ; Queiroz, Marcia Silva ^{[3, 5]}

Affiliation

^[1] Univ Sao Paulo, Fac Med Sci, Lipids Lab LIM 10, Sao Paulo - Brazil

^[2] Univ Sao Judas Tadeu, Sao Paulo - Brazil

^[3] Nove Julho Univ Uninove, Dept Grad Med, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Clin Hosp, Med Sch, Lab Carbohydrates & Radioimuneassays LIM 18, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Internal Med Dept, Endocrinol Div, Med Sch, Sao Paulo - Brazil

• Document type: Journal article
• Source: JOURNAL OF DIABETES AND ITS COMPLICATIONS; v. 35, n. 9 SEP 2021.
• Web of Science Citations: 0

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 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. (AU)

• 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