Dietary Monounsaturated Fatty Acids Promote Aortic Atherosclerosis in LDL Receptor-Null, Human ApoB100-Overexpressing Transgenic Mice

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 18; no. 11; pp. 1818 - 1827
• Main Authors: Rudel, Lawrence L, Kelley, Kathryn, Sawyer, Janet K, Shah, Ramesh, Wilson, Martha D
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01-11-1998; Hagerstown, MD Lippincott
• Subjects: Analysis of Variance; Animals; Aortic Diseases - etiology; Apolipoprotein B-100; Apolipoproteins B - genetics; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Coronary Artery Disease - etiology; Dietary Fats - adverse effects; Fatty Acids, Unsaturated - adverse effects; Gene Expression Regulation - physiology; Humans; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Particle Size; Receptors, LDL - genetics; Pathogenesis; Rodentia; Monounsaturated fatty acid; Transgenic animal; Cardiovascular disease; Supplemented diet; Cholesterol; Vascular disease; Lipoprotein LDL; Vertebrata; Mammalia; Mouse; Animal; Atherosclerosis; Risk factor; Aorta; Biological receptor
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/01.atv.18.11.1818

In mice with genetically engineered high levels of plasma low density lipoprotein (LDL), we tested the hypothesis that an increase in the dietary content of monounsaturated fatty acids but not of polyunsaturated fatty acids would promote atherosclerosis. The mouse model used was an LDL receptor-null, human apoB100-overexpressing strain. Six experimental groups of 19 to 38 mice of both sexes were established when the animals had reached 8 weeks of age. For the next 16 weeks, individual groups were fed either a commercial diet or prepared diets including fat as 10% of energy, with 5 different fatty acid enrichment patterns including the followingsaturated (sat), cis and trans monounsaturated (mono), and n-3 and n-6 polyunsaturated (poly). Highly significant differences (ANOVA, P<0.0001) in LDL cholesterol (in mg/dL) were found, with the rank order at 16 weeks being trans mono (mean, 1390)>sat (922)=cis mono (869)=n-6 poly (868)>n-3 poly (652)>commercial diet (526). Significant elevations in very low density lipoprotein cholesterol were also found in the trans and cis mono and sat groups, and triacylglycerol concentrations were also elevated in all groups. High density lipoprotein cholesterol concentrations were consistently low (20 to 50 mg/dL) in all groups. Highly significant differences (ANOVA, P<0.0001) in atherosclerosis, quantified by measurement of aortic cholesteryl ester concentration (mg/g protein) among dietary fatty acid groups were found, with the order being trans mono (mean, 50.4)>sat (35.6)=cis mono (34.6)>n-6 poly (18.3)=n-3 poly (9.7)=commercial diet (7.8). Therefore, in this mouse model of hypercholesterolemia, dietary cis or trans monounsaturated fat did not protect against atherosclerosis development, whereas aortic atherosclerosis in either of the polyunsaturated fat groups was significantly less than in the saturated fat group. (Arterioscler Thromb Vasc Biol. 1998;18:1818-1827.)