Arterial intimal retention of pro-atherogenic lipoproteins in insulin deficient rabbits and rats

Recent observations that remnants of triglyceride rich lipoproteins become trapped within the subendothelial of arterial vessels gives rise to the pos sibility that these particles could initiate the atherogenic cascade. Incre ased frequency and progression of atherosclerosis in diabetes might in part be a consequence of raised concentrations in plasma of remnant lipoprotein s. In addition, diabetes may lead to changes in the arterial vasculature wh ich exacerbate arterial retention of pro-atherogenic lipoproteins. To explo re these possibilities, in this study we determined aortic retention of chy lomicron remnants, which are of intestinal origin, and of hepatically deriv ed low-density lipoproteins (LDL) in insulin deficient rabbits and rats. Th e two species were selected because of their disparate susceptibility to de velop atherosclerosis in the presence of diabetes induced hyperlipidemia. C hylomicron remnants and LDL were differentially radiolabelled with a residu al marker and injected simultaneously into conscious rabbits or rats. Arter ial retention was determined 2 h after injection, and relative retention wa s 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 sig nificantly greater than in non-diabetic control groups. In contrast, insuli n deficiency did not influence arterial retention of LDL. Rabbits which are susceptible to diabetes induced atherogenesis had significantly greater in timal 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 atheroscleroti c susceptibility might be related to degree of remnant entrapment within th e subendothelial space. Greater retention of remnant lipoproteins could in part explain the increased prevalence of atherogenesis in diabetes. (C) 200 0 Elsevier Science Ireland Ltd. All rights reserved.