Vascular injury has been shown to induce proliferation and apoptosis in vascular smooth muscle cells (VSMCs), and this balance between cell growth and cell death will ultimately influence the size of the injury-induced lesion. Apoptotic cell death has been documented in human atherectomy and endarterectomy specimens and in a number of animal models of vessel wall stenosis. Recently, they have shown that as early as 30 minutes following balloon injury VSMCs of rat carotid and rabbit iliac arteries undergo apoptotic cell death at a high frequency as demonstrated by TUNEL staining, and by the appearance of condensed chromatin and other morphological features characteristic of apoptosis in electron micrographs. This induction of apoptosis coincides with a marked downregulation of the bcl-X protein, a potential cell death antagonist. Their data suggest that VSMC apoptosis is a rapid and prominent cellular response to acute vascular wall injury, the extent of this apoptotic response may ultimately influence characteristics of the lesion that result from the insult. To more fully understand the regulation and the role of apoptosis in vessel wall lesion formation, it is proposed to: 1) determine the frequencies of VSMC apoptosis in single injury and double-injury model of angioplasty in rabbit external iliac arteries; 2) assess the effects of enhanced apoptosis on vessel lesion formation using a replication defective adenovirus encoding Fas ligand; 3) characterize apoptosis in a mouse model of arterial injury; and 4) study the mechanisms that coordinate cell cycle and apoptosis at a molecular level.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG015052-01
Application #
2451079
Study Section
Pathology A Study Section (PTHA)
Program Officer
Finkelstein, David B
Project Start
1998-01-01
Project End
2002-12-31
Budget Start
1998-01-01
Budget End
1998-12-31
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
St. Elizabeth's Medical Center of Boston
Department
Type
DUNS #
073797292
City
Boston
State
MA
Country
United States
Zip Code
01235
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