ENDOTHELIAL CELLS

Project: Research project

Project Details

Description

Studies have been initiated to understand the molecular basis of
endothelial cell growth regulation. We have isolated from human
endothelial cell extracellular matrix a heparan sulfate
proteoglycan which binds and potentiates the mitogenic activity
of acidic fibroblast growth factor. Our hypothesis states that
human endothelial cells synthesize into the extracellular matrix a
heparan sulfate proteoglycan which binds and sequester growth
factors such as acidic fibroblast growth factor. The extracellular
matrix heparan sulfate proteoglycan modulates the mitogenic
potential of acidic fibroblast growth factor. The acidic fibroblast
growth factor, in turn, controls the synthesis and/or turnover of
the extracellular matrix heparan sulfate proteoglycan which binds
the growth factors and thus modualtes the interaction of the
growth factors with the endothelial cells. The extracellular
matrix heparan sulfate proteoglycan, as well as the carbohydrate
side chains and the core protein will be isolated and structurally
characterized. The structure of the acidic fibroblast growth
factor binding region in the extracellular matrix heparan sulfate
proteoglycan will be elucidated. In order to determine if the
heparan sulfate proteoglycan increases the affinity of acidic
fibroblast growth factor for the fibroblast growth factor receptor,
the interaction of extracellular matrix heparan sulfate
proteoglycan and acidic fibroblast growth factor will be further
investigated. The capacity of the isolated extracellular matrix to
bind acidic fibroblast growth factor and potentiate endothelial
cell growth will be studied. We will evaluate the hypothesis that
acidic fibroblast growth factor controls the synthesis and turnover
of extracellular matrix heparan sulfate proteoglycan which binds
and potentiates the mitogenic activity of acidic fibroblast growth
factor. Finally, we will elucidate the structural and functional
relationship between the cellular heparan sulfate proteoglycans
which binds acidic fibroblast growth factor and the extracellular
matrix heparan sulfate proteoglycan which binds acidic fibroblast
growth factor. This proposal will test a hypothesis that will
provide new information on the growth regulation of human
endothelial cells.
StatusFinished
Effective start/end date7/1/886/30/92

Funding

  • National Institutes of Health
  • National Institutes of Health: $131,281.00
  • National Institutes of Health

ASJC

  • Medicine(all)

Fingerprint Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.