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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:2423-2429.)
© 1997 American Heart Association, Inc.

Articles

Local Application of LDL Promotes Intimal Thickening in the Collared Carotid Artery of the Rabbit

Katelijne E. Matthys; Cor E. Van Hove; Mark M. Kockx; Luc J. Andries; Nancy Van Osselaer; Arnold G. Herman; ; Hidde Bult

From the Divisions of Pharmacology (K.E.M., C.E. Van H., N. Van O., A.G.H., H.B.) and Physiology (L.J.A.), University of Antwerp, and the Department of Pathology, General Hospital Middelheim, (M.M.K.), Antwerp, Belgium.

Correspondence to Katelijne E. Matthys, Division of Pharmacology, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium. E-mail matthysk{at}uia.ua.ac.be

Abstract Oxidized LDL (oxLDL) has been implicated in atherogenesis on the basis of in vitro studies and is present in atherosclerotic lesions. The aim of this study was to investigate the effects of LDL and oxLDL on intimal thickening in vivo. Intimal thickening was evoked by the placement of silicone collars around the carotid arteries of rabbits for 2 weeks. The collars were connected to osmotic minipumps containing LDL (7 µg h^-1, n=16 arteries), oxLDL (Cu²⁺ oxidized, 7 µg h^-1, n=16), or phosphate-buffered saline (5 µL h^-1, n=16). Segments proximal to the collars served as controls. Collar placement without lipoprotein application resulted in the appearance of -SMC actin–immunoreactive cells in the intima, thereby increasing the intimal thickness from 5±1 to 26±5 µm. The perivascular infusion of LDL or oxLDL within the collar significantly enhanced the development of the intima ninefold and sevenfold, respectively. The large intimas resulting from lipoprotein exposure were infiltrated by macrophages and T lymphocytes, and the intimal collagen area was increased from 5±2% in the discrete collar-induced intima to 20% in the lipoprotein-evoked lesions. In conclusion, the local vascular application of LDL, oxidized in vitro or possibly in vivo, elicited an inflammatory-fibroproliferative response characteristic of arteriosclerotic lesions, thereby demonstrating an active role for this class of lipoproteins in the disease process.

Key Words: LDL • intima • atherosclerosis • collagen • leukocyte

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