Lipoprotein lipase deficiency and CETP in streptozotocin-treated apoB-expressing mice.
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.
Kako
Yuko
Y
Department of Medicine, Columbia University, New York, NY 10032, USA.
Massé
Maureen
M
Huang
Li-Shin
LS
Tall
Alan R
AR
Goldberg
Ira J
IJ
D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics / Q000378:metabolism*; D001161:Arteriosclerosis / Q000209:etiology* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D053480:Cholesterol Ester Transfer Proteins; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D006023:Glycoproteins; D006801:Humans; D008071:Lipoprotein Lipase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D051379:Mice; D011994:Recombinant Proteins / Q000378:metabolism
D001055:Apolipoproteins B; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D008074:Lipoproteins; D011994:Recombinant Proteins; D008071:Lipoprotein Lipase