verbatim): Re-endothelialization (rET) at sites of spontaneous or iatrogenic disruption has classically been considered to result from the migration and proliferation of endothelial cells (ECs) from endothelium adjacent to the site of injury, including endothelium lining the branch vessels which originate within the injured vascular segment. Preliminary data from our laboratory and others', however, suggests that neighboring ECs may not constitute the exclusive basis for endothelial repair. These studies suggest that circulating cells derived from the bone marrow (BM) and exhibiting phenotypic features of ECs are capable of homing to sites of arterial injury and incorporating into neoendothelium. Accordingly, the goal of the studies outlined in this proposal is to delineate the contribution of BM-derived endothelial progenitor cells (EPCs) to the maintenance and repair of vascular endothelium. The proposed experiments have been designed to test specific hypotheses, organized according to three Specific Aims. The first Specific Aim is to establish definitive evidence regarding the BM origin of EPCs which incorporate into neoendothelium. These experiments will be performed in murine and rodent models of arterial injury following transplantation of BM from Tie2/LacZ transgenic mice to immunodeficient animals.
Specific Aim 2 is designed to investigate the impact of systemic pathology on EPC kinetics and incorporation.
Specific Aim 3 is organized to explore the impact of EC mitogens, EC antagonists, and genetic engineering on EPC incorporation into neoendothelium.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL057516-07
Application #
6638464
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Program Officer
Sopko, George
Project Start
1997-01-01
Project End
2005-04-30
Budget Start
2003-05-01
Budget End
2004-04-30
Support Year
7
Fiscal Year
2003
Total Cost
$372,492
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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