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Papers In Press, published online ahead of print June 1, 2002
Department of Medicine, Columbia University, New York, NY 10032
1 To whom correspondence should be addressed. e-mail: ijg3{at}columbia.edu
Both hyperglycemia and hyperlipidemia have been postulated to increase atherosclerosis in patients with diabetes mellitus. To study the effects of diabetes on lipoprotein profiles and atherosclerosis in a rodent model, we crossed mice that express human apolipoprotein B (HuB), mice that have a heterozygous deletion of lipoprotein lipase (LPL1), and transgenic mice expressing human cholesteryl ester transfer protein (CETP). Lipoprotein profiles due to each genetic modification were assessed while mice were consuming a Western type diet. Fast-protein liquid chromatography analysis of plasma samples showed that HuB/LPL1 mice had increased VLDL triglyceride, and HuB/LPL1/CETP mice had decreased HDL and increased VLDL and IDL/LDL. All strains of mice were made diabetic using streptozotocin (STZ); diabetes did not alter lipid profiles or atherosclerosis in HuB or HuB/LPL1/CETP mice.
In contrast, STZ-treated HuB/LPL1 mice were more diabetic, severely hyperlipidemic due to increased cholesterol and triglyceride in VLDL and IDL/LDL, and had more atherosclerosis.
Abbreviations: CTR, control; HSPG, heparan sulfate proteoglycan; HuB, human apolipoprotein B; LPL1, a heterozygous deletion of lipoprotein lipase; LRP, LDL receptor-related protein; RAGE, receptor for advanced glycosylation endproducts; STZ, streptozotocin; UC, area under the curve; WTD, a Western type diet
Supplementary key words diabetes • hypercholesterolemia • lipoproteins • glucose
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