Comparative endocrinology-paracrinology-autocrinology of human adult large vessel endothelial and smooth muscle cells |
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Authors: | Hiroyoshi Hoshi Mikio Kan Jan-Kan Chen Wallace L McKeehan |
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Institution: | (1) W. Alton Jones Cell Science Center, Inc., 10 Old Barn Road, 12946 Lake Placid, New York |
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Abstract: | Summary Endothelial and smooth muscle cells were isolated from human adult large blood vessels to compare their proliferative response
to hormones and growth factors. Neural extracts and the medium from differentiated hepatoma cells were used as concentrated
sources of required hormones and growth factors that supported both cell types. Active hormones and growth factors were identified
from the neural extracts and hepatoma medium by substitution or direct isolation and biochemical characterization. Epidermal
growth factor, lipoproteins, and heparin-binding growth factors elicited growth-stimulatory effects on both endothelial and
smooth muscle cells. Both types of human vascular cells displayed 7600 to 8600 specific heparin-binding growth factor receptors
per cell with a similar apparent dissociation constant (Kd) of 200 to 250 pM. Heparin modified the response of both endothelial and smooth muscle cells to heparin-binding growth factors dependent on
the type of heparin-binding growth factor and amount of heparinlike material present. In addition, heparin exerted a growth
factor-independent inhibition of smooth muscle cell proliferation. Platelet-derived growth factor, insulinlike growth factors,
and glucocorticoid specifically supported proliferation of smooth muscle cells with no apparent effect on endothelial cell
proliferation. Growth-factorlike proteinase inhibitors had an impact specifically on endothelial cell proliferation. Transforming
growth factor beta was a specific inhibitor of endothelial cells, but had a positive effect on smooth muscle cell proliferation.
The results provide a framework for differential control of the two vascular cell types at normal and atherosclerotic blood
vessel sites by the balance among positive and negative effectors of endocrine, paracrine and autocrine origin.
This research was supported by NIH grants CA37589, HL33847, and AM35310 from the National Institutes of Health, Bethesda,
MD; grant 1718 from the Council for Tobacco Research; and a grant from RJR/Nabisco, Inc. |
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Keywords: | growth factors endothelial cells smooth muscle cells atherosclerosis aging protease inhibitors |
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