Advanced glycation: a novel outlook on atherosclerosis.
Atherosclerosis is a major global cause of morbidity and mortality, and diabetes patients are at increased risk of coronary heart disease development. Advanced glycation of proteins occurs in the body due to raised concentrations of reducing sugars and reactive oxygen species, and is a causal factor behind complications of diabetes. Glycated proteins, through alteration of protein structure and function, and from ligation with their receptors, lead to widespread vascular damage. The alpha-oxoaldehyde, methylglyoxal (MG) is the most reactive glycation precursor, and is increased in the blood of diabetes patients. There is debate about the triggering events leading to atherosclerosis, but the inflammatory action of glycated proteins, including those with MG adducts, through their receptor, RAGE, is a major candidate for initiating plaque formation. In addition glycation may cause cross-links on proteins of the extracellular matrix, stiffening arteries and 'trapping' other macromolecules. MG is also likely to form adducts on many other proteins, enzymes, lipids, DNA or RNA, changing their structure, and may disrupt enzyme activity, hormone regulation and immune function. In the latter context, MG disrupts function of the potent antigen presenting cells, dendritic cells. This effect may be a double edged sword: Poor control of infections may contribute to persistent inflammation, whilst inhibition of immune activation by dendritic cells may inhibit plaque progression. This review aims to present these ideas as a novel slant on the role of the glycation process in atherosclerosis.
Price
C L
CL
Antigen Presentation Research Group, Imperial College London Faculty of Medicine, North West London Hospitals campus, Watford Road, Harrow, Middlesex, HA1 3UJ, UK.
Knight
S C
SC
D000818:Animals; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D001424:Bacterial Infections / Q000150:complications / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D048909:Diabetes Complications / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D007333:Insulin Resistance / Q000276:immunology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D011765:Pyruvaldehyde / Q000378:metabolism*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction
D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D011765:Pyruvaldehyde; D003546:Cysteine Endopeptidases; D020782:Matrix Metalloproteinases