Inhibition Of Cholesterol Atherosclerosis In Rabbits By Amino Imino Propene Diacetate
Previous studies have shown that in vitro blockage of the ε amino group of lysine in LDL by acetoacetylation enhances LDL uptake by macrophages and liver cells and inhibits uptake of LDL by fibroblasts in tissue culture. Amino imino propene diacetate (AIPD) is a compound which is absorbed into the blood after feeding and which blocks the ε amino group of lysine in LDL for short periods of time after which the AIPD dissociates from LDL and is excreted in the urine. AIPD does not inhibit absorption of either 14C labelled or unlabelled cholesterol from the gastrointestinal tract. In a preliminary study it was found that 19 rabbits fed 300 mg crude AIPD along with 500 mg cholesterol per day in their food for 14 weeks showed 13.0 ± 3.3 (mean ± S.E.) % of their total aortic intimal surface area covered with grossly visible atherosclerotic plaques. In comparison 13 control rabbits fed 500 mg cholesterol per day in their food for 14 weeks showed 33.9 ± 6.0% of their total aortic intimal surface area covered with atherosclerotic plaques. (P< 0.01) These in vivo observations suggest that the inhibition of atherosclerosis by AIPD might be related to a reduction in the number of free lysine amino groups in LDL. In previous studies, we reported that dietary induced lysine deficiency could inhibit atherosclerosis. These and other studies suggest that blocking or reducing the number of free lysine ε, amino groups in LDL appears to enhance LDL uptake and clearance by liver and macrophage type cells and reduces LDL uptake by arterial smooth muscle cells and fibroblasts in vivo. The combination of these effects appears to offer some protection against the development of cholesterol atherosclerosis.