Human population studies have established that plasma high density lipoprotein (HDL) cholesterol levels are associated with a decreased risk of cardiovascular disease. HDLs have a number of cardioprotective properties, including an ability to inhibit inflammation in multiple cell types involved in atherosclerotic lesion development such as endothelial cells, smooth muscle cells and macrophages.
HDLs also have anti-diabetic and anti-oxidant properties. In addition to inhibiting the oxidation of atherogenic low density lipoproteins (LDLs), HDLs and apoA-I, the main HDL apolipoprotein, also inhibit the high glucose-induced formation of reactive oxygen species in macrophages. However, HDLs and apoA-I from people with type 2 diabetes mellitus (T2DM) inhibit reactive oxygen species formation in macrophages less effectively that HDLs from healthy individuals. The attenuated anti-oxidant properties of HDLs from people with T2DM has been attributed to the non-enzymatic glycation of HDL apolipoproteins. In addition to reducing the capacity of HDLs to inhibit oxidative stress in macrophages, non-enzymatic glycation of HDL apolipoproteins also impairs the anti-inflammatory properties and other cardioprotective functions of HDLs.