Abstract 285: The Effects of Hypercholesterolemia and Lipoprotein-Cholesterol Concentrations on Angiotensin II-Induced Abdominal Aortic Aneurysms

Abstract

Background and objective Angiotensin II (AngII) infusion promotes abdominal aortic aneurysms (AAA) in both normo- and hypercholesterolemic mice, but the latter have a greater susceptibility, implicating a role of hypercholesterolemia in AngII-induced AAA. A recent publication demonstrated that high-density lipoprotein (HDL) administration prevented AngII-induced AAA in apoE -/- mice without affecting total plasma cholesterol concentrations. The purpose of this study was to determine the relationship between concentrations and characteristics of plasma cholesterol and lipoproteins and AngII-induced AAA. Methods and Results Three strains of male mice were studied: C57BL/6, LDL receptor -/-, and apoE -/-. These mice were fed either a normal diet or a saturated fat- enriched diet. AngII (1 μg/kg/min) was infused for 4 weeks through osmotic minipumps implanted subcutaneously. Total plasma cholesterol concentrations were measured using an enzymatic kit. Lipoproteins were resolved by size exclusion gel chromatography and non-HDL and HDL analyzed using Peakfit software. AAA was quantified by measuring maximal outer width of suprarenal aortas. In C57BL/6 mice, the fat-enriched diet modestly increased concentrations of total plasma cholesterol (114 ± 4 vs 99 ± 6 mg/dl; P=0.03) and HDL-C (98 ± 4 vs 81 ± 7 mg/dl; P=0.02), while did not change non-HDL-C/HDL-C ratio (0.21 ± 0.03 vs 0.24 ± 0.03; P=0.5) and AAA (1.1 ± 0.1 vs 1.1 ± 0.1 mm; P=0.6). In LDL receptor -/- mice, the fat-enriched diet feeding increased concentrations of total plasma cholesterol (1590 ± 58 vs 276 ± 9 mg/dl; P< 0.001), HDL-C (132 ± 5 vs 90 ± 3 mg/dl; P<0.001), non-HDL-C/HDL-C ratio (10.8 ± 0.3 vs 2.1 ± 0.1; P<0.001), and AAA (1.6 ± 0.1 vs 1.2 ± 0.1 mm; P=0.002), compared to LDL receptor -/- mice fed the normal diet. In apoE -/- mice, the fat-enriched diet increased concentrations of total plasma cholesterol (1261 ± 121 vs 348 ± 38 mg/dl; P<0.001), had no effect on HDL-C, increased non-HDL-C/HDL-C ratio (53.1 ± 5.9 vs 10.5 ± 2.0; P=0.016), and had no effect on AAA development (1.5 ± 0.2 vs 1.6 ± 0.2 mm; P=0.4). Conclusion Hypercholesterolemia promotes AngII-induced AAA, while AAA has no clear relationship with either concentrations of total plasma cholesterol or HDL-C.