HDL Protein Turnover as a Link Between Cardiac Disease and Diabetes

The vascular complications following hyperglycemia and hyperlipidemia are detrimental to individuals that suffer from diabetes mellitus as it accelerates atherosclerosis of the coronary arteries, and the fibrosis of the myocardium. Hyperglycemia causes abnormalities in insulin action and secretion as well as has an effect on biochemical pathways. This leads to alterations of signal transduction pathways and protein function. Prolonged exposure to hyperglycemia can cause glycation of proteins. Changes in the function of lipoprotein metabolism due to glycation, is one of the main issues increasing the risk for developing atherosclerosis. It impairs cholesterol metabolism, and excess cholesterol builds up in arteries and is no longer able to be removed via the reverse cholesterol transport pathway. The purpose of this study is to understand why diabetes contributes to cardiac disease. This study helps to prove the hypothesis that the stability of HDL proteins is smaller and their synthesis rates much faster in hyperglycemic conditions. Thus, impairing their effectiveness in functioning. To study HDL metabolism in T2DM and how to apply 2H2O metabolism labeling, the lab developed an algorithm that allows for the calculation of the enrichment of intracellular amino acid based on body water enrichment analysis. The results of this experimental design showed very strong correlation between hyperglycemia and increased clearance of HDL where HDL is not able to remove cholesterol adequately in the reverse cholesterol transport.