ATHEROSCLEROSIS AND GLYCATION

Atherosclerosis is the major cause of death in the industrialised worl d. Though much work on the pathogenesis of atherosclerosis points to ' oxidised' low density lipoprotein (LDL) as a key aeitological feature in the generation of the atherosclerotic plaque, the nature of this 'o xidised' LDL iir vivo remains an enigma. We argue here that glycated L DL shows many of the characteristics attributed to 'oxidised LDL' and may be the source of the latter in vivo. These include the increased u ptake and impaired degradation of glycated LDL by macrophages and the stimulation of transendothelial chemotaxis of monocytes, cytokine secr etion and platelet aggregation. We hypothesise that the covalent bindi ng of glycated LDL to the endothelial cell wall may result in the form ation of the early atherosclerotic lesion of the fatty streak and that apolipoprotein E may mediate the physiological clearance of glycated moieties. The proposed role of glycation in the pathogenesis of athero sclerosis would explain its high incidence among diabetics and the con tentious epidemiological and experimental correlations between dietary sugar and atherosclerosis.