LOCAL APPLICATION OF LDL PROMOTES INTIMAL THICKENING IN THE COLLARED CAROTID-ARTERY OF THE RABBIT

Oxidized LDL (oxLDL) has been implicated in atherogenesis on the basis of in vitro studies and is present in atherosclerotic lesions. The ai m of this study was to investigate the effects of LDL and oxLDL on int imal thickening in vivo. Intimal thickening was evoked by the placemen t of silicone collars around the carotid arteries of rabbits for 2 wee ks. The collars were connected to osmotic minipumps containing LDL (7 mu g h(-1), n=16 arteries), oxLDL (Cu2+ oxidized, 7 mu g h(-1), n=16), or phosphate-buffered saline (5 mu L h(-1), n=16). Segments proximal to the collars served as controls. Collar placement without lipoprotei n application resulted in the appearance of alpha-SMC actin-immunoreac tive cells in the intima, thereby increasing the intimal thickness fro m 5+/-1 to 26+/-5 mu m. The perivascular infusion of LDL or oxLDL with in the collar significantly enhanced the development of the intima nin efold and sevenfold, respectively. The large intimas resulting from li poprotein exposure were infiltrated by macrophages and T lymphocytes, and the intimal collagen area was increased from 5+/-2% in the discret e collar-induced intima to approximate to 20% in the lipoprotein-evoke d lesions. In conclusion, the local vascular application of LDL, oxidi zed in vitro or possibly in vivo, elicited an inflammatory-fibroprolif erative response characteristic of arteriosclerotic lesions, thereby d emonstrating an active role for this class of lipoproteins in the dise ase process.