Denimal Damien, Monier Serge, Bouillet Benjamin, Vergès Bruno, Duvillard Laurence
INSERM, UMR1231, University of Burgundy, 21000 Dijon, France.
Department of Biochemistry, CHU Dijon Bourgogne, 21000 Dijon, France.
Metabolites. 2023 Feb 9;13(2):253. doi: 10.3390/metabo13020253.
Alterations affecting high-density lipoproteins (HDLs) are one of the various abnormalities observed in dyslipidemia in type 2 diabetes mellitus (T2DM) and obesity. Kinetic studies have demonstrated that the catabolism of HDL particles is accelerated. Both the size and the lipidome and proteome of HDL particles are significantly modified, which likely contributes to some of the functional defects of HDLs. Studies on cholesterol efflux capacity have yielded heterogeneous results, ranging from a defect to an improvement. Several studies indicate that HDLs are less able to inhibit the nuclear factor kappa-B (NF-κB) proinflammatory pathway, and subsequently, the adhesion of monocytes on endothelium and their recruitment into the subendothelial space. In addition, the antioxidative function of HDL particles is diminished, thus facilitating the deleterious effects of oxidized low-density lipoproteins on vasculature. Lastly, the HDL-induced activation of endothelial nitric oxide synthase is less effective in T2DM and metabolic syndrome, contributing to several HDL functional defects, such as an impaired capacity to promote vasodilatation and endothelium repair, and difficulty counteracting the production of reactive oxygen species and inflammation.
影响高密度脂蛋白（HDL）的改变是2型糖尿病（T2DM）和肥胖症血脂异常中观察到的各种异常之一。动力学研究表明，HDL颗粒的分解代谢加速。HDL颗粒的大小、脂质组和蛋白质组均发生显著改变，这可能是导致HDL一些功能缺陷的原因。关于胆固醇流出能力的研究结果不一，从缺陷到改善都有。多项研究表明，HDL抑制核因子κB（NF-κB）促炎途径的能力较弱，随后单核细胞在内皮上的黏附及其向内皮下间隙的募集也会减少。此外，HDL颗粒的抗氧化功能减弱，从而促进氧化型低密度脂蛋白对血管系统的有害作用。最后，在T2DM和代谢综合征中，HDL诱导的内皮型一氧化氮合酶激活效果较差，这导致了HDL的多种功能缺陷，如促进血管舒张和内皮修复的能力受损，以及难以对抗活性氧的产生和炎症反应。
