Aminoguanidine has an anti-atherogenic effect in the cholesterol-fed rabbit.
Advanced glycosylation endproducts (AGEs) which result from the non-enzymatic interaction of proteins and glucose are implicated in the vasculopathy of diabetes and aging. Since aminoguanidine (A) inhibits the accumulation of AGEs, we explored its effects on the development of atherosclerosis. Male New Zealand white cross rabbits fed a high cholesterol (1%) diet were randomized to control (C) or increasing doses of A treatment (25, 50 and 100 mg/kg A body weight). The animals were sacrificed after 12 weeks. Sudan IV was used to stain the lipid containing plaques of the aortic arch, thoracic and abdominal aorta and the surface area occupied by atheroma was assessed. Increasing doses of A treatment were associated with reduction in plaque formation in the aorta. At a dose of 100 mg/kg A, there was a 30, 49 and 48% reduction in plaque formation in the aortic arch, thoracic and abdominal aorta, respectively. There was a correlation between AGE levels and the degree of atheroma in these cholesterol fed rabbits (control, r = 0.75, P < 0.01; 100 mg/kg A, r = 0.59, P = 0.02). These data suggest that advanced glycation may participate in atherogenesis and raise the possibility that inhibitors of advanced glycation may retard this process.
Panagiotopoulos
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S
Department of Medicine, Austin and Repatriation Medical Centre (Austin Campus), University of Melbourne, Heidelberg, Australia. sianna@austin.unimelb.edu.au
O'Brien
R C
RC
Bucala
R
R
Cooper
M E
ME
Jerums
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G
D000818:Animals; D001161:Arteriosclerosis / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006146:Guanidines / Q000097:blood / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008297:Male; D010865:Pilot Projects; D011817:Rabbits; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D002791:Cholesterol, Dietary; D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D006146:Guanidines; D008055:Lipids; D017392:Thiobarbituric Acid Reactive Substances; D002784:Cholesterol; C004479:pimagedine