Reduction in tissue LDL accumulation during coronary artery regression in cynomolgus macaques

The aim of this study was to determine whether the amount of LDL that had accumulated in the coronary arteries of cynomolgus monkeys during an 18-month period on a hypercholesterolemic (H) diet was reduced during subsequent periods of 6 and 12 months on a normolipemic (N) diet. This was performed by assessing the accumulation of LDL in the left anterior descending (LAD) branch of the left coronary artery within an area 4 mm from its origin, since this region contained the largest lesions in the LAD. LDL accumulation was estimated by measuring the percent cross-sectional area of artery occupied by reaction product depicting apo B by an immunoperoxidase procedure. The following reduction in mean (+/- SD) percent cross-sectional area occupied by reaction product was found in 8 animals on the progression diet (group I), 7 animals on the 6-month regression diet (group II), and 9 animals on the 12-month regression diet (group III), respectively: 21.7 +/- 4.7, 6.9 +/- 5.5, and 2.3 +/- 1.3. Differences between group I and either group II or III were statistically significant (using the Wilcoxon signed-ranks test). In group I, LDL was localized primarily in the necrotic core and around pools of foam cells. In groups II and III fewer foam cells and smaller pools of extracellular debris were qualitatively evident, and LDL was localized closer to the lumen and along collagen fibers. These results suggest that lowering of the plasma LDL level following termination of a hypercholesterolemic diet also induces a decrease in the LDL content in coronary artery lesions, even without significant reductions in lesion size, and that this decrease might be responsible for the decrease in foam cells.