American Society for Biochemistry and Molecular Biology
Journal of Lipid Research vol:51 issue:6 pages:1478-1485
OBJECTIVES: The aim of this study was to investigate the hypothesis that the relative atherogenicity of VLDL and LDL particles is dependent on the topographic site.
BACKGROUND: Apolipoprotein B-containing lipoproteins are a risk factor for atherosclerosis and ischemic vascular diseases but whether remnant lipoproteins or LDL are more pro-atherogenic remains a matter of debate. Clinical observations in patients with type III hyperlipoproteinemia and familial hypercholesterolemia suggest that topography may modulate the relative atherogenicity of VLDL and LDL.
METHODS: Atherosclerosis was compared at four topographic sites in homozygous LDL receptor (LDLr) deficient rabbits fed normal chow and heterozygous LDLr deficient rabbits with the same genetic background fed a 0.15% cholesterol diet to match plasma cholesterol levels.
RESULTS: Separation of lipoproteins by ultracentrifugation showed that VLDL cholesterol was significantly higher and LDL cholesterol significantly lower in LDLr+/- diet rabbits compared to LDLr-/- rabbits. The intima/media ratio in the ascending thoracic aorta and in the abdominal aorta at the level of the renal arteries was 1.5-fold (p<0.05) higher in LDLr-/- rabbits than in LDLr+/- diet rabbits whereas no difference was observed in the descending thoracic aorta and in the abdominal aorta just above the bifurcation. Differences remained statistically significant after adjustment for plasma cholesterol, plasma triglycerides, and sex, indicating that relative content of VLDL and LDL cholesterol affects atherosclerosis dependent on the topographic site. Compositional differences of lesions between both hyperlipidemia models were also site-dependent.
CONCLUSION: Topographic factors determine the relative atherogenicity of VLDL and LDL.