Oxidized low-density lipoprotein enhances intimal thickening and alters vascular reactivity

Oxidized low density lipoprotein (oxLDL) is present in atherosclerotic lesions and has been implicated in the etiopathogenesis of atherosclerosis mainly based on in vitro studies. In view of the lack of data on the activity of oxLDL in vivo, we decided to study its effects in the rabbit by local application at the level of the vascular wall. Intimal thickening was evoked by the placement of a silicone collar around the carotid arteries during 2 weeks. The collar was connected to an osmotic minipump containing human oxLDL (7 micrograms h-1), LDL (7 micrograms h-1) or phosphate-buffered saline. Collar placement resulted in a thickening of the intima thereby increasing the thickness from 5 +/- 1 to 26 +/- 5 microns with the appearance of alpha-actine positive smooth muscle cells. Perivascular infusion of LDL or oxLDL significantly enhanced the intima, containing large amounts of T-lymphocytes, collagen and smooth muscle cells. The placement of the collar and the infusion of oxLDL during 14 days resulted in an increased sensitivity to serotonin and a decreased sensitivity to acetylcholine. The maximal relaxation to acetylcholine was reduced by 50% whereas the endothelium-independent relaxation to nitroglycerin were not affected. These results show for the first time that the local application of oxLDL in vivo promotes intimal thickening and impairs the endothelium-dependent relaxations thereby supporting the suggestion that oxLDL plays an important role in the morphological and functional changes present in atherosclerotic blood vessels.