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 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.
Proctor
S D
SD
University Department of Medicine, Royal Perth Hospital, Box X2213 GPO, Perth, Australia.
Pabla
C K
CK
Mamo
J C
JC
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D002914:Chylomicrons / Q000378:metabolism / Q000493:pharmacokinetics; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D004195:Disease Models, Animal; D007328:Insulin / Q000097:blood / Q000172:deficiency; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000493:pharmacokinetics; D008297:Male; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013311:Streptozocin; D017539:Tunica Intima / Q000378:metabolism* / Q000473:pathology
D002914:Chylomicrons; D007328:Insulin; D008077:Lipoproteins, LDL; D013311:Streptozocin