title: Effects of diabetes and CETP expression on diet-induced atherosclerosis in LDL receptor-deficient mice.
abstract: The role of CETP expression and diabetes in atherogenesis was investigated in mice with heterozygous disruption of the LDL receptor gene (LDLR1). LDLR1 mice with and without CETP expression were treated with streptozotocin (STZ) and maintained on a standard diet for one month before switching to an atherogenic diet for an additional month. STZ-sensitive mice had approximately 2.5-fold higher glycemia and 7.5- to 8.0-fold higher cholesterolemia. Factorial analysis of variance showed no significant effect of diabetes, CETP or diabetes-CETP interaction on the size of the atherosclerotic lesions. CETP expression in non-diabetic mice resulted in a 50% reduction in the area of the atherosclerotic lesions. Multiple regression analysis showed a positive and independent atherogenic effect of triglyceridemia in LDLR1 mice and of cholesterolemia in diabetic mice. Logistic analysis showed that elevated plasma cholesterol level significantly increased the risk of developing large lesion size (>75th percentile). In conclusion, CETP expression did not alter the lesion formation in response to diabetes, although it may be protective in the euglycemic state; the triglyceride level was an independent risk factor for LDL receptor-deficient mice but not for CETP-expressing mice; and elevated plasma cholesterol levels increased the risk of developing large atherosclerotic lesions, independently of CETP and diabetes.
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.
authors.forename: Jairo A
authors.initials: JA
authors.lastname: Berti
authors.forename: Alessandro G
authors.initials: AG
authors.lastname: Salerno
authors.forename: Eliete J B
authors.initials: EJ
authors.lastname: Bighetti
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Casquero
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Boschero
authors.forename: Helena C F
authors.initials: HC
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D004036:Diet, Atherogenic; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008055:Lipids / Q000097:blood; D051379:Mice; D011973:Receptors, LDL / Q000172:deficiency*; D012044:Regression Analysis
chemical_list: D001786:Blood Glucose; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D008055:Lipids; D011973:Receptors, LDL