Abstract
To evaluate whether the relative atherogenicity of VLDL and LDL is dependent on the topographic site, atherosclerosis was compared at four topographic sites in homozygous LDL receptor (LDLr)-deficient rabbits fed normal chow and in heterozygous LDLr-deficient rabbits with the same genetic background fed a 0.15% cholesterol diet to match cholesterol levels. VLDL cholesterol was significantly higher and LDL cholesterol significantly lower in LDLr(+/-) diet rabbits compared with LDLr(-/-) rabbits. Intimal area in the ascending thoracic aorta and in the abdominal aorta at the level of the renal arteries was 1.4-fold (P < 0.05) and 1.5-fold (P < 0.05) higher, respectively, in LDLr(-/-) rabbits than in LDLr(+/-) diet rabbits, whereas no significant difference occurred in the descending thoracic aorta and in the abdominal aorta just above the bifurcation. Differences remained statistically significant after adjustment for plasma cholesterol, triglycerides, and sex. Compared with LDLr(+/-) diet rabbits, higher intimal lipoprotein lipase (LPL) and apolipoprotein (apo) B levels were observed in LDLr(-/-) rabbits only at the level of the descending thoracic aorta. Intimal apo E levels in LDLr(-/-) rabbits were significantly lower in sites with a larger intima than in LDLr(+/-) diet rabbits. In conclusion, the relative atherogenicity of VLDL and LDL is dependent on the topographic site.
Highlights
To evaluate whether the relative atherogenicity of very low-density lipoproteins (VLDLs) and LDL is dependent on the topographic site, atherosclerosis was compared at four topographic sites in homozygous LDL receptor (LDLr)-deficient rabbits fed normal chow and in heterozygous LDLr-deficient rabbits with the same genetic background fed a 0.15% cholesterol diet to match cholesterol levels
The relative atherogenicity of VLDL and LDL is dependent on the topographic site Atherosclerosis was quantified at the age of 21 months in the ascending thoracic aorta, the descending thoracic aorta at the level of the ligamentum arteriosum, the abdominal aorta at the level of the renal arteries, and the abdominal aorta just above the bifurcation
Because the main difference between LDLr+/Ϫ diet rabbits and LDLrϪ/Ϫ rabbits is the amount of VLDL and LDL cholesterol, the data in Table 3 suggest that the relative atherogenicity of VLDL and LDL is dependent on the topographic site
Summary
To evaluate whether the relative atherogenicity of VLDL and LDL is dependent on the topographic site, atherosclerosis was compared at four topographic sites in homozygous LDL receptor (LDLr)-deficient rabbits fed normal chow and in heterozygous LDLr-deficient rabbits with the same genetic background fed a 0.15% cholesterol diet to match cholesterol levels. VLDL cholesterol was significantly higher and LDL cholesterol significantly lower in LDLr+/؊ diet rabbits compared with LDLr؊/؊ rabbits. Compared with LDLr+/؊ diet rabbits, higher intimal lipoprotein lipase (LPL) and apolipoprotein (apo) B levels were observed in LDLr؊/؊ rabbits only at the level of the descending thoracic aorta. Frank Jacobs and Yingmei Feng are postdoctoral fellows of the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen. Because many patients have elevated levels of both larger remnants and smaller LDL particles, intrinsic differences in the relative atherogenicity of these particles are difficult to analyze in humans. Because most of plasma cholesterol is packed in smaller LDL particles in LDLrdeficient apo B100-only mice and in larger VLDL in apo Abbreviations: apo, apolipoprotein; IDL, intermediate density lipoprotein; LDLr, LDL receptor. Vascular apo E expression results in pleiotropic antiatherogenic effects such as stimulation of reverse cholesterol transport, antioxidant activity, antiproliferative effects on T-lymphocytes, and inhibition of smooth muscle cell proliferation [9,10,11,12,13]
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