The clinical utility of small caliber prosthetic arterial grafts is most often limited by stenosis due to intimal hyperplasia. Although it is now widely appreciated that this lesion results from abnormal proliferation of cells, the signals that initiate this hyperplastic response are largely unknown. Previous research has often focused on the platelet, activated by interaction with biomaterials or by altered hemodynamics, as the source of proliferative stimuli. However, it is now apparent that monocytes and endothelial cells can also produce mitogens that stimulate the proliferation of smooth muscle cells and fibroblasts. The role of these two cell types in the hyperplastic response to vascular grafts has heretofore recieved little attention. Accordingly, our initial Specific Aims will focus on the interactions of prosthetic materials with human monocytes or vascular endothelium in relation to the hyperplastic response.
SPECIFIC AIM 1 : WE WILL TEST THE HYPOTHESIS THAT WELL CHARACTERIZED BIOMATERIALS SUCH AS DACRON, AND EXPANDED POLYTETRAFLUOROETHYLENE (ePTFE), AND NHLBI REFERENCE STANDARDS STIMULATE THE PRODUCTION BY HUMAN MONONUCLEAR PHAGOCYTES OF GROWTH FACTORS AND/OR INFLAMMATORY MEDIATORS SUCH AS INTERLEUKIN-1.
SPECIFIC AIM 2 : WE WILL TEST THE HYPOTHESIS THAT MONOCYTES ADHERE TO CLINICALLY USED CARDIOVASCULAR BIOMATERIALS SUCH AS DACRON OR (ePTFE) IN VITRO AND TO GRAFT MATERIALS IMPLANTED CHRONICALLY IN BABOONS AFTER THEY DEVELOP A CELLULAR LINING.
SPECIFIC AIM 3 : WE WILL TEST THE HYPOTHESIS THAT EXPOSURE TO BIOMATERIALS SUCH AS ePTFE OR DACRON STIMULATES PRODUCTION BY HUMAN ENDOTHELIAL OF ACTIVITY THAT PROMOTES THE GROWTH OF SMOOTH MUSCLE CELLS AND/OR FIBROBLASTS. THIS ENDOTHELIAL FUNCTION, ALREADY KNOWN TO BE INDUCED BY CERTAIN INJURIOUS STIMULI, MIGHT CONTRIBUTE TO FAILURE EVEN IF GRAFTS ARE SUCCESSFULLY SEEDED WITH ENDOTHELIUM.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL036898-02
Application #
3352252
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1987-04-01
Project End
1992-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Tufts University
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02111
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