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Abstract
Restenosis as a result of neointimal smooth muscle cell accumulation is an important
limitation to the effectiveness of balloon angioplasty as a treatment for end-stage
atherosclerosis. Quantitative animal models allow the definition of pathophysiological
mechanisms and the evaluation of new therapeutic strategies. In this study we quantified
the time course of neointima formation by morphometry, and smooth muscle cell (SMC)
proliferation by immunocytochemistry for proliferating cell nuclear antigen (PCNA),
in the pig carotid artery 0-28 days following balloon injury. This led to two distinct
kinds of injury observed also in clinical studies, namely medial dilatation or deep
medial tearing with rupture of the internal elastic lamina. Dilatation injury alone
led to medial enlargement and neointima formation by 7 days, which did not increase
further up to 28 days. Medial enlargement was similar following rupture of the internal
elastic lamina; however the sum of neointima formation plus the area of medial repair
(‘neomedia’) increased progressively up to 21 days after balloon injury. Balloon injury
increased the PCNA index of smooth muscle cells in the media underlying an intact
internal elastic lamina maximally after 3 days. The PCNA index in the neointima and
especially in the neomedia was greater and maximal after 7 days. Endothelial regrowth
occurred by 21 days in the presence or absence of medial tears. Our results establish
a quantitative pig model of balloon injury which will allow the assessment of new
therapeutic strategies directed at two clinically relevant types of injury. Medial
tearing is associated with an enhanced and localized proliferative response and may
therefore be especially important in human restenosis.
Keywords
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Article info
Publication history
Accepted:
February 23,
1995
Received in revised form:
February 17,
1995
Received:
August 12,
1994
Footnotes
☆This work was supported by British Heart Foundation Grant No. 90/94. PHG and APB were supported by British Heart Foundation Junior Research Fellowships.
Identification
Copyright
© 1995 Published by Elsevier Inc.
