Abstract

Pathologic process in which the endothelial cell plays a key role are a leading cause of death in man. Cultured human endothelial cells (HEC) in serum-free medium will be used for long-term study of the endocrine control of growth, function and aging of the human vasculature. Two growth factors, one from neural tissue and one from liver cells, will be isolated and characterized. As much of the N-terminal amino acid sequence as possible will be determined for each factor by gas phase sequencing. Monospecific antibody and DNA probes will be prepared based on the sequencing information. These reagents will be used to isolate recombinant bacterial clones containing the cDNA coding for growth factor mRNA. The monospecific antibody and cDNA probes will be used to analyze the sites and regulation of synthesis of the two types of HEC growth factors. Primary emphasis will be on a rigorous test of the hypothesis that liver is an important endocrine organ in the biology of endothelial cells. Hepatocytes are an important source of an HEC maintenance and regeneration factor. Hormonal regulation of the synthesis and secretion of the factor in cultured liver cells will be elucidated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL033847-03
Application #
3346118
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1986-01-08
Project End
1988-12-31
Budget Start
1988-01-01
Budget End
1988-12-31
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Adirondack Biomedical Research Institute
Department
Type
DUNS #
City
Lake Placid
State
NY
Country
United States
Zip Code
12946

  Publications

Mansson, P E; Malark, M; Sawada, H et al. (1990) Heparin-binding (fibroblast) growth factors type one and two genes are co-expressed in proliferating normal human vascular endothelial and smooth muscle cells in culture. In Vitro Cell Dev Biol 26:209-12
Hoshi, H; Kan, M; Chen, J K et al. (1988) Comparative endocrinology-paracrinology-autocrinology of human adult large vessel endothelial and smooth muscle cells. In Vitro Cell Dev Biol 24:309-20
Miller-Davis, S; McKeehan, W; Carpenter, G (1988) Prostatropin and acidic FGF also support proliferation of an EGF-dependent keratinocyte cell line. Exp Cell Res 179:595-9
Hoshi, H; Kan, M; Mioh, H et al. (1988) Phorbol ester reduces number of heparin-binding growth-factor receptors in human adult endothelial cells. FASEB J 2:2797-800
DiSorbo, D; Shi, E G; McKeehan, W L (1988) Purification form human hepatoma cells of a 130-kDa membrane glycoprotein with properties of the heparin-binding growth factor receptor. Biochem Biophys Res Commun 157:1007-14
Grunz, H; McKeehan, W L; Knochel, W et al. (1988) Induction of mesodermal tissues by acidic and basic heparin binding growth factors. Cell Differ 22:183-9
Kan, M; DiSorbo, D; Hou, J Z et al. (1988) High and low affinity binding of heparin-binding growth factor to a 130-kDa receptor correlates with stimulation and inhibition of growth of a differentiated human hepatoma cell. J Biol Chem 263:11306-13
Knochel, W; Born, J; Hoppe, P et al. (1987) Mesoderm-inducing factors. Their possible relationship to heparin-binding growth factors and transforming growth factor-beta. Naturwissenschaften 74:604-6
McKeehan, W L; Adams, P S; Fast, D (1987) Different hormonal requirements for androgen-independent growth of normal and tumor epithelial cells from rat prostate. In Vitro Cell Dev Biol 23:147-52
McKeehan, W L; Crabb, J W (1987) Isolation and characterization of different molecular and chromatographic forms of heparin-binding growth factor 1 from bovine brain. Anal Biochem 164:563-9

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