Human endothelial cells possess multiple phenotypes in vitro. These phenotypes include the traditional monolayer phenotype, the differentiated phenotype represented by the organized, three dimensional tubular structures, the revertant phenotype which is induced by a transition from the differentiated phenotype to the monolayer phenotype and the modulated phenotype represented by the morphological change induced by gamma-interferon (gIF). The expression of these phenotypes are relevant to atherogenesis since the modulation of any phenotype results in significant changes in the levels of mRNA transcripts for sis and FN. We propose to extend these observations by expanding the number of mRNA markers which characterize these endothelial cell phenotypes at the transcriptional and translational levels. We also hope to further elucidate the mechanism(s) by which gIF mediates the formation of the modulated phenotype and uncouples ECGF-induced endothelial cell proliferation. In addition, we propose that each human endothelial cell phenotype possesses mRNA transcripts which are unique to the expression of the individual phenotype. It is our intent to establish cloned cDNA's which represent RNA molecules absent from or reduced in the monolayer phenotype but present or enhanced in the differentiated phenotype. The identity of a few of these specific cDNA clones will be established by sequence analysis and inserted into the monolayer phenotype using an inducible viral vector. The contribution of these induced polypeptide(s) to alterations in the morphology of the monolayer phenotype will be assessed in anticipation of further defining the pathway of endothelial cell non-terminal differentiation. These studies promise to significantly contribute to our understanding of atherogenesis, especially the contribution mediated by the human endothelial cell.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL035627-05
Application #
3349661
Study Section
(SRC)
Project Start
1987-01-01
Project End
1990-09-29
Budget Start
1988-09-30
Budget End
1989-09-29
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost
Name
American National Red Cross
Department
Type
DUNS #
003255213
City
Washington
State
DC
Country
United States
Zip Code
20037
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