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 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<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.

中文翻译：

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氨基甲酰化修饰的血清白蛋白损害糖尿病肾病中巨噬细胞胆固醇外流

背景和目标

脂质代谢异常、尿毒症毒素积累和晚期糖基化终产物可能导致动脉粥样硬化恶化。本研究描述了从糖尿病肾病患者中分离的血清白蛋白的糖基化和氨基甲酰化谱及其对胆固醇流出的影响。

材料与方法

49 名患有 2 型糖尿病 (T2DM) 和不同 eGFR 的患者通过 ELISA 测量血浆中的羧甲基赖氨酸 (CML) 和氨基甲酰化蛋白 (CBL)、比色法测量血浆中的同型瓜氨酸 (HCit) 来评估糖基化和氨基甲酰化谱。在分离的白蛋白中，我们通过荧光定量 CBL (ELISA) 和总 AGE 和戊糖苷。用分离的白蛋白处理巨噬细胞，并测量由 HDL ₂或 HDL _3介导的¹⁴ C-胆固醇流出。Kruskal-Wallis 检验、Jonckheere-Terpstra 检验和 Brunner 后测用于组间比较。

结果

血浆中 CML、HCit、CBL 的测定，如白蛋白中的总 AGE 和戊糖苷，组间没有差异；然而，在 CKD 的更晚期阶段，分离白蛋白中的 CBL 较高（p  =  0.0414）。与由HDL ² ( p = 0.0288 )和HDL _{3 (} p < ^_ 0.0001)，以及与 eGFR ≥60 mL/min/1.73m ² per HDL ₂ ( p =         0.0001) 和 HDL ₃ ( p  <  0.0001)。治疗 48 小时表明，与对照组和其他 CKD 组相比，eGFR<15  mL/min/1.73m ^{2的 HDL} _2介导的¹⁴ C-胆固醇流出百分比较低（ p = 0.0274）。  

结论

 从患有 T2DM 和 eGFR<60 mL/min/1.73m ²的个体中分离的白蛋白遭受更大的氨甲酰化，并且它们会损害由 HDL ₂和 HDL ₃介导的胆固醇流出。反过来，这可以促进巨噬细胞中的脂质积累和反向胆固醇转运的障碍。