THE ENDOTHELIUM DURING CUFF-INDUCED NEOINTIMA FORMATION IN THE RABBITCAROTID-ARTERY

Intimal thickening in human arteries is considered as a site of predil ection for atherosclerosis. The placement of a flexible, physically no nconstrictive, silicone cuff around the rabbit carotid artery induced a neointima composed of smooth muscle cells (SMCs) within 14 days. To investigate possible alterations of the endothelial cells (ECs) during neointima formation, their morphology was examined with scanning elec tron microscopy (SEM), transmission electron microscopy (TEM), and con focal microscopy. In the early postoperative period (6 hours), both cu ffed and sham-operated arteries demonstrated small foci (5 to 200 mu m ) of denudation, presumably as a consequence of the manipulation. With in 24 hours the luminal surface of the cuffed and sham-operated arteri es was completely covered with endothelium, which remained continuous throughout the study. However, after 1 week the ECs of the cuffed arte ries contained a pronounced rough endoplasmic reticulum. From 6 hours until 3 days, polymorphonuclear leukocytes infiltrated the cuffed but not the sham-operated arteries from the lumen. Subendothelial SMC accu mulation in the cuffed arteries began after this time period. At day 1 4 a full-blown neointima composed of longitudinally oriented SMCs had formed in the cuffed arteries. The sham operated arteries did not deve lop a neointima. During neointima formation immunoreactivity for von W illebrand factor (vWf) increased in the ECs, and vWf was deposited in the extracellular spaces of the neointima. At day 14 the area of vWf d eposits correlated positively with the area of the neointima (r=.73, P <.001). In subsequent weeks, the intimal area did not increase, and vW f deposits vanished from the neointimal matrix. The endothelium of the sham-operated arteries showed no change in vWf immunoreactivity compa red with untreated arteries throughout the study. The altered ultrastr uctural morphology of the ECs and the concurrent vWf deposition in cuf fed but not in sham-operated arteries point to alterations in EC funct ion during the development of the neointima. The vWf secretion could p ossibly lead to increased adhesiveness of the extracellular matrix for the ECs as well as modulate neointima formation.