A. Arias-Alvarado, S. Ilchenko, E. Reed, S. Kashyap, T. Kasumov
Northeast Ohio Medical University,
United States
Keywords: diabetes, biomarker, cardiovascular complications, glycation, lipoprotein ApoA1
Summary:
Cardiovascular diseases (CVD) are the major cause of morbidity and mortality in patients with diabetes. The CVD complications of diabetes are related to continuously elevated blood glucose levels. Diabetes is associated with both reduced HDL levels and dysfunction, the known risk factors for CVD. Glycation of HDL proteins may contribute to HDL dysfunction and CVD in diabetes. During hyperglycemia, glucose reacts with the lysine (K) residues of proteins to form Amadori-glycation adducts (AGAs). In contrast to the well-characterized effects of Advanced Glycation End-products (AGEs), the degradation products of AGAs, the role of early AGA in HDL functions, and CVD complications of diabetes are poorly understood. We tested the hypothesis that hyperglycemia-induced glycation contributes to HDL dysfunction and CVD in patients with type 2 diabetes (T2D). HDL from patients with T2D and matched healthy controls (n=10/group) was isolated and its anti-oxidant and cholesterol efflux properties were quantified. HDL proteome composition and post-translational modification of proteins were quantified by proteomics approach. Metabolic 2H2O-labeling was applied to quantify HDL proteome dynamics. Patients with T2D and controls had similar lipid (triglycerides, total cholesterol, and HDL cholesterol) profile. HDL from T2D patients had reduced anti-oxidant activity and macrophage-cholesterol efflux capacity (P