High-density lipoproteins (HDL) originate as discoidal particles that are rapidly converted by
lecithin:cholesterol acyltransferase (LCAT) into the spherical particles that predominate in normal human plasma. Spherical HDL consist of multiple populations of particles that vary widely in size, composition and function. Human population studies have established that high plasma
HDL cholesterol levels are associated with a reduced incidence of
cardiovascular disease. The mechanistic basis of this relationship is not well understood, but most likely involves a number of the cardioprotective functions of HDL. These include the ability of
apolipoprotein (
apo) A-I, the main
apolipoprotein constituent of HDL, to remove
cholesterol from macrophages in the artery wall. HDL also have
antioxidant and anti-inflammatory properties that are potentially cardioprotective. Evidence that some of these beneficial properties are compromised in people with diabetes and renal disease is emerging. Persistently elevated plasma
glucose levels in people with diabetes and poor
glycemic control can lead to irreversible, non-enzymatic glycation of
plasma proteins, including
apoA-I. Non-enzymatically
glycated proteins are also prevalent in people with diabetes and
end-stage renal disease who are at high cardiovascular risk. Evidence that non-enzymatically glycated
apoA-I inhibits the LCAT reaction and impairs some of the cardioprotective properties of HDL is also emerging. This review is concerned with how non-enzymatic glycation of
apoA-I affects the ability of LCAT to convert discoidal HDL into spherical HDL, how it affects
cholesterol efflux from macrophages and how it affects the anti-inflammatory and
antioxidant properties of HDL.