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.