Glycation of the lipoprotein ApoAI is a novel biomarker for early predicting diabetic cardiovascular complications.

S. Kashyap, S. Ilchenko, E. Reed, T. Kasumov
Northeast Ohio Medical University,
United States

Keywords: diabetes, CVD, HDL, ApoAI, glycation, biomarker


Cardiovascular diseases (CVD) is the major cause of morbidity and mortality in patients with diabetes. Although glycated hemoglobin (HbA1) levels and CVD risk are linearly correlated, currently no biomarker is available to inform and mechanistically link hyperglycemia to CVD pathogenesis during diabetes development. HDL and ApoAI, the major protein of HDL, exert anti-atherogenic functions, including anti-oxidant, anti-inflammation, and reverse cholesterol transport. Diabetes is associated with both reduced HDL levels and dysfunction, which are amongst the known risk factors for CVD. The modification of HDL proteins through glycation results in HDL dysfunction in diabetes. During events of hyperglycemia the glucose reacts with the lysine residues of proteins to form Amadori-glycation adducts (AGAs) which may decompose and generate Advanced Glycation End-products (AGEs) involved in aging and complications of diabetes. We tested the hypothesis that hyperglycemia-induced glycation contributes to HDL dysfunction and CVD in patients with type 2 diabetes (T2D). We further evaluated Amadori glycated ApoAI as a biomarker that reflects the glycation process and that is involved in the pathogenesis of diabetic CVD. The HDL from patients with T2D and healthy controls (n=10/group) was isolated and the anti-oxidant and cholesterol efflux properties were quantified. HDL proteome composition were quantified by proteomics aproach. Patients from both cohorts (T2D and control) had similar HDL cholesterol levels. However, the HDL from T2D patients had reduced anti-oxidant activity and macrophage-cholesterol efflux capacity (P