Biomarkers associated with high-density lipoproteins in atherosclerotic kidney disease.
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.
Lipid Research Group, Centre for Vascular Research, Level 3, Lowy Centre, The University of New South Wales, Sydney, NSW, 2052, Australia, k.rye@unsw.edu.au.
Kerry-Anne
KA
Rye
D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D000975:Antioxidants / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000517:prevention & control; D002784:Cholesterol / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism*
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000975:Antioxidants; D016632:Apolipoprotein A-I; D015415:Biomarkers; D008075:Lipoproteins, HDL; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase