Deposition pattern of monocytes and fatty streak development in hypercholesterolemic rabbits

Abstract

To further characterize the role of monocytes in atherogenesis, we studied the influence of a qualitatively, well-defined hemodynamic flow field on the deposition pattern of monocytes in the thoracic aorta of normal (N, n = 6) and hypercholesterolemic (H, n = 10) rabbits. Pairs of H rabbits were sacrificed after 1, 2, 4, 7 and 10 weeks of cholesterol feeding. Complete deposition patterns of adherent cells were quantified over 500 mm 2 of aortic endothelium around the lesion-susceptible intercostal orifices using an en face light microscopic technique. Adherent cells were almost exclusively monocytes by morphological criteria and non-specific esterase staining. The mean density of adherent cells in normal rabbits was 1.28 ± 1.21 (S.D.) per mm 2 of endothelium and increased nearly 5-fold by 7 weeks of cholesterol feeding. High local densities of adherent monocytes (up to 34 cells/mm 2) were noted over early fatty lesions present in one 4 week and all 7 and 10 week H rabbits. Adherent cell densities near intercostal orifices prior to lesion formation were ~50% greater than in non-orifice regions in both the normal and the 1 and 2 week H rabbit groups. These differences were statistically significant at P < 0.05 by ANOVA. We conclude that preferred adherence of monocytes occurs around intercostal orifices in normolipidemic and early cholesterol-fed rabbits before lesions develop at these lesion-prone sites. Monocyte deposition appears to be governed not only by the arterial flow field but also by cholesterol feeding since higher numbers of adherent monocytes were found on both early fatty streaks and nonlesioned endothelium in rabbits fed cholesterol for longer than 4 weeks.