[Proteins modified with glycation or oxidation products accelerate atherosclerosis in experimental...

To investigate whether advanced glycation end products (AGE) or advanced oxidative protein products (AOPP) contributes to atherogenesis in experimental hypercholesterolemic rabbits.

Hypercholesterolemic (0.5% wt/wt diet) rabbits received repeated intravenous injections of either AGE modified rabbit serum albumin (AGE-RSA) or AOPP modified RSA (AOPP-RSA) for 10 weeks. Three control groups were set as follows: a group fed with high cholesterol diet alone, a group fed with high cholesterol diet and injected with normal RSA, and a group fed with normal diet. The animals were sacrificed and aortas were dissected and stained with Sudan red IV. Atheromatous plaques in the aortas en face were evaluated by computer-assisted morphometry and by histologic examination. Hematological parameters (triglyceride, cholesterol, AGE and AOPP) were also tested.

(1) The relative plaque area in rabbits receiving repeated injections of AGE or AOPP was 50.1%+/-7.4% and 62.4%+/-8.8% respectively, both were significantly larger than either that of hypercholesterolemic rabbits (29.8%+/-6.3%, P<0.05) or that of hypercholesterolemic rabbits injected with unmodified RSA (20.9%+/-6.4%, P<0.05). In aortic arch, thoracic aorta and abdominal aorta, atherosclerotic lesions in AGE group and AOPP group were more severe than in any of the control groups. (2)The average thickness of the plaques on thoracic aortas in AGE group [(138.1+/-13.0) microm] and in AOPP group [(147.7+/-13.1) microm ] were significantly thicker than either of that in the group treated with hypercholesterolemic diet alone [(85.7+/-15.0) microm] or that in the group treated with non modified RSA [(95.5+/-15.7) microm]. (3) Glyceride and cholesterol levels in all animals on hypercholesterolemic diet were similar. AGE and AOPP serum levels in groups injected with AGE or AOPP were significantly higher than that in any of the control groups. AGE serum concentrations were positively correlated with the atheromatous plaque area(r=0.408, P=0.005), so were the AOPP serum concentrations (r=0.595, P=0.000).

AGE or AOPP modified proteins accelerate the formation of atherosclerosis and may contribute to the accelerated atherosclerosis in end stage renal diseases.