Recent observations that remnants of
triglyceride rich
lipoproteins become trapped within the subendothelial of arterial vessels gives rise to the possibility that these particles could initiate the atherogenic cascade. Increased frequency and progression of
atherosclerosis in diabetes might in part be a consequence of raised concentrations in plasma of remnant
lipoproteins. In addition, diabetes may lead to changes in the arterial vasculature which exacerbate arterial retention of pro-atherogenic
lipoproteins. To explore these possibilities, in this study we determined aortic retention of
chylomicron remnants, which are of intestinal origin, and of hepatically derived
low-density lipoproteins (
LDL) in insulin deficient rabbits and rats. The two species were selected because of their disparate susceptibility to develop
atherosclerosis in the presence of diabetes induced
hyperlipidemia.
Chylomicron remnants and
LDL were differentially radiolabelled with a residual marker and injected simultaneously into conscious rabbits or rats. Arterial retention was determined 2 h after injection, and relative retention was expressed as a percentage of mean arterial exposure. We found in
insulin deficient rabbits and rats that intimal and medial retention of
chylomicron remnants was positively related to the degree of
hyperglycemia and was significantly greater than in non-diabetic control groups. In contrast,
insulin deficiency did not influence arterial retention of
LDL. Rabbits which are susceptible to diabetes induced
atherogenesis had significantly greater intimal retention of
chylomicron remnants compared to rats. Results from this study support the hypothesis that chronic
hyperglycemia promotes arterial retention of
triglyceride rich remnant
lipoproteins and that atherosclerotic susceptibility might be related to degree of remnant entrapment within the subendothelial space. Greater retention of remnant
lipoproteins could in part explain the increased prevalence of
atherogenesis in diabetes.