Circulation, Vol 84, 755-767, Copyright © 1991 by American Heart Association
FF Weidinger, JM McLenachan, MI Cybulsky, JT Fallon, NK Hollenberg, JP Cooke and P Ganz
BACKGROUND. We studied the effects on and possible interaction of balloon
denudation and hypercholesterolemia on large arteries in the rabbit with
special regard to structure and vascular reactivity. METHODS AND RESULTS.
New Zealand White rabbits fed a 1% cholesterol diet or a standard diet for
14 weeks underwent balloon denudation of the left iliac artery 4 weeks
before death. Both the balloon-injured and the control iliac arteries were
harvested for in vitro studies of vascular reactivity, for
immunohistochemical staining with monoclonal antibodies directed at smooth
muscle cells and macrophages, and for scanning electron microscopy. Balloon
injury caused intimal smooth muscle proliferation with little macrophage
infiltration and was followed by recovery of endothelium-dependent
vasodilator function within 4 weeks. Hypercholesterolemia caused
macrophage-rich lesions confined to the intima with moderate impairment of
endothelial vasodilator function. Balloon injury in the setting of
hypercholesterolemia caused intimal smooth muscle cell proliferation and
intense macrophage infiltration throughout the arterial wall and severe
impairment of endothelial vasodilator function. Scanning electron
microscopy confirmed regrowth of the endothelium in all balloon-injured
vessels. In the balloon-injured arteries of hypercholesterolemic animals,
the regenerated endothelium exhibited areas of atypical morphology not seen
after balloon injury or hypercholesterolemia alone. CONCLUSIONS. The
present study shows that balloon injury, hypercholesterolemia, and their
combination cause distinct lesions and functional disturbances. An arterial
balloon injury in the setting of hypercholesterolemia produces a diffuse
inflammatory response that is accompanied by a sustained impairment of
endothelial function and a marked proliferative response.
ARTICLES
Hypercholesterolemia enhances macrophage recruitment and dysfunction of regenerated endothelium after balloon injury of the rabbit iliac artery
Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115.
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