A decline in prostacyclin production with age has been observed in organisms, intact blood vessels and cells in culture from rats or humans. The long term objective of this research is to determine what changes occur at the cellular level in the aging blood vessel which cause this decline. Specifically we will culture aortic endothelial cells, smooth muscle cells and fibroblasts from rats at various ages. We will determine changes which occur with age in the incorporation of the prostaglandin precursor arachidonate into lipid stores in these cells. We will determine if changes occur with age in the binding of bradykinin (a hormone which stimulates prostaglandin production), or if changes occur with age in response to bradykinin in phospholipid methylation, Ca++ flux, or phospholipase activation. We will determine changes with age in the inactivation of endothelial cell endoperoxide synthetase during synthesis of protaglandins and in the ability of this cell to recover the activity of this enzyme after its inactivation. The activity of prostacyclin synthetase and the production of hydroperoxy fatty acids which inactivate prostacyclin synthetase will be determined in the cells as a function of blood vessel age. Methodology will include cell culture, radioimmunoassay and thin layer chromatography. Prostacyclin plays an important role in blood vessel dilation and in the inhibition of platelet aggregation. An understanding of the mechanisms which cause the decline with age in prostacyclin synthesis by cells from blood vessels could lead to rational approaches to therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG005007-02
Application #
3115555
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1984-08-01
Project End
1987-07-31
Budget Start
1985-08-01
Budget End
1986-07-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Boston University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code