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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:1499-1505.)
© 1999 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Atrophic Remodeling of the Artery-Cuffed Artery

Ilana M. Bayer; S. Lee Adamson; B. Lowell Langille

From the Toronto Hospital Research Institute (I.M.B., B.L.L.); the Samuel Lunenfeld Research Institute (S.L.A.), Mount Sinai Hospital; and the Departments of Laboratory Medicine and Pathobiology (I.M.B., B.L.L.), Physiology (I.M.B., S.L.A.), and Obstetrics and Gynecology (S.L.A., B.L.L.), University of Toronto, Toronto, Ontario, Canada.

Correspondence to B. Lowell Langille, CCRW 1-836, The Toronto Hospital (General Division), 200 Elizabeth St, Toronto, Ontario, M5G 2C4, Canada. E-mail lowell.langille{at}utoronto.ca

Abstract—Increased arterial wall tension stimulates growth and remodeling of arteries, but little is known about the effects of decreased wall tension, despite its developmental and pathological significance. Consequently, we cuffed 1 carotid artery in rabbits with a portion of the contralateral artery to off-load circumferential wall tension. The model produced rapid and extensive atrophy of the cuffed artery that yielded decreases in the DNA content of the cuffed artery (a measure of cell number) from 8.0±0.5 µg/cm of in situ vessel length to 5.6±0.5 µg/cm at 21 days postoperatively. The elastin content of the cuffed artery was also significantly reduced, from 399±17 to 283±17 µg/cm, and collagen content was reduced from 468.0±59.0 to 154±24 µg/cm (P<0.05) at 21 days postoperatively. Detection of DNA oligonucleosomes by gel electrophoresis implicated apoptotic cell death in remodeling due to cuffing. Upregulation of matrix metalloproteinases (MMPs), including MMP-2, MMP-9, and unidentified gelatinases, indicated that these enzymes may also be involved in remodeling. No further changes in wall structure were seen between 3 weeks and 6 months, and the excised artery that was used as a cuff exhibited normal medial morphology for at least 6 months postoperatively. We infer from these experiments that off-loading of arterial wall tension induces rapid and extensive atrophy of the arterial media.

Key Words: apoptosis • extracellular matrix • matrix metalloproteinase • wall tension

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