Carbamylated lipoproteins in diabetes

Abstract

Diabetic dyslipidemia is characterized by quantitative and qualitative abnor-malities in lipoproteins. In addition to glycation and oxidation, carbamylation is also a post-translational modification affecting lipoproteins in diabetes. Patients with type 2 diabetes (T2D) exhibit higher levels of carbamylated low-density lipoproteins (cLDL) and high-density lipoproteins (cHDL). Accumulating evidence suggests that cLDL plays a role in atherosclerosis in diabetes. cLDL levels have been shown to predict cardiovascular events and all-cause mortality. cLDL facilitates immune cell recruitment in the vascular wall, promotes accumulation of lipids in macrophages, and contributes to endothelial dysf-unction, endothelial nitric oxide-synthase (eNOS) inactivation and endothelial repair defects. Lastly, cLDL induces thrombus formation and platelet aggregation. On the other hand, recent data have demonstrated that cHDL serum level is independently associated with all-cause and cardiovascular-related mortality in T2D patients. This relationship may be causative since the atheroprotective properties of HDL are altered after carbamylation. Thus, cHDL loses the ability to remove cholesterol from macrophages, to inhibit monocyte adhesion and recruitment, to induce eNOS activation and to inhibit apoptosis. Taken together, it seems very likely that the abnormalities in the biological functions of LDL and HDL after carbamylation contribute to atherosclerosis and to the elevated cardiovascular risk in diabetes.

Keywords: Carbamylation; Lipoprotein; Diabetes; Low-density lipoprotein; High-density lipoprotein; Myeloperoxidase

Core Tip: There is growing evidence that carbamylation of lipoproteins occurring in diabetes contributes to the pathophysiology of atherosclerosis, and therefore plays a role in the cardiovascular risk. Numerous studies have demonstrated that carbamylated low-density lipoproteins (LDL) is more atherogenic than native LDL, citing, for instance, its role in foam cell formation or ability to damage endothelial function. In addition, carbamylated high-density lipoproteins exhibits reduced antiatherogenic properties, especially in terms of the capacity to induce cholesterol efflux from macrophages and to protect endothelium.