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(Circulation. 1997;96:4333-4342.)
© 1997 American Heart Association, Inc.

Articles

Remodeling and Neointimal Formation in the Carotid Artery of Normal and P-Selectin–Deficient Mice

Anjali Kumar, PhD; Jennifer L. Hoover, BS; Carol A. Simmons, BS; Volkhard Lindner, MD, PhD; ; Ronald J. Shebuski, PhD

From Cardiovascular Pharmacology, Pharmacia and Upjohn, Inc, Kalamazoo, Mich, and Department of Surgery, Maine Medical Center Research Institute, South Portland (V.L.). Dr. Kumar is currently at Preclinical R & D Genetics Institute, Andover, Me.

Correspondence to Ronald J. Shebuski, PhD, Pharmacia and Upjohn, Inc, 301 Henrietta St, Kalamazoo, MI 49007. E-mail akumar{at}genetics.com

Background Inflammatory reactions such as leukocyte activation with platelet adherence and release of inflammatory mediators occur after percutaneous transluminal coronary angioplasty and may play a role in restenosis. Vascular remodeling with neointimal formation was studied in normal C57Bl/J6 and P-selectin–deficient mice.

Methods and Results The left common carotid artery was ligated just proximal to the carotid bifurcation. Four weeks later, left carotids and contralateral controls were snap-frozen. Computer-aided morphometry was performed to measure ratios of neointimal to medial area (NI/M) in 10 sections per animal as a measure of the thickness of the neointimal lesion. For normal mice, NI/M was 1.13±0.2 (n=20), whereas NI/M was reduced by 76% to 0.27±0.1 (n=19) in P-selectin knockout mice. Vascular constriction (as measured by the length of external elastic lamina) was the same in both groups, but the circumference of the lumen in knockout mice was 26% larger. Also, normal and P-selectin–deficient mice were killed at 3 and 7 days after ligation (n=6 for each group per time point). Histological staining and immunostaining for CD45 showed no inflammatory cell presence in P-selectin knockout mice. However, in normal mice, leukocyte infiltration was observed in the adventitia, media, and developing neointima. Also, P-selectin immunostaining was observed in media and developing neointima of normal mice.

Conclusions These data suggest that P-selectin is involved in processes leading to cell migration and proliferation associated with vascular remodeling, presumably by mediating leukocyte recruitment and the interaction between platelets and leukocytes.

Key Words: restenosis • immunohistochemistry • remodeling • cells

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