Recruitment and dynamics of leukocytes in the formation of arterial intimal thickening--a comparative study with normo- and hypercholesterolemic rabbits.

Leukocyte involvement in intimal thickening was investigated as a function of time and diet. Fibromuscular or foam cell-rich thickings were induced by electrical stimulation (ES) of carotid arteries in rabbits either on a normal or a high (1%) cholesterol diet. Under both dietary conditions granulocytes (predominantly neutrophils), monocytes and lymphocytes migrated through and accumulated beneath a continuous, yet structurally altered endothelium already after 1 day of ES. This preceded the occurrence of smooth muscle cells (SMCs) in the intima. Under normocholesterolemia, leukocyte attachment to the endothelium decreased with continued ES, which coincided with the re-establishment of a normal endothelial cell pattern. Neutrophils ceased to invade the stimulated intima and disappeared from the lesion after 14 days. The proportion of mononuclear leukocytes was also reduced in the thickened intima, finally amounting to 5.5 +/- 5.9% in the 4-week-old fibromuscular lesion where SMCs prevailed. Hypercholesterolemia did not affect neutrophil involvement in response to ES. However, it provoked lipid deposition first in macrophages, then in SMCs and resulted in elevated amounts of mononuclear leukocytes both within the foam cell-rich thickening and in association with the overlying endothelium. These data indicate adaptive behavior of leukocytic infiltration in the development of fibromuscular thickening, and a shift to a chronic inflammatory response under additional hypercholesterolemia.