Characterization of pulmonary smooth muscle cell growth activity from hypoxic pulmonary endothelial cells

CHEST Journal ◽  
1988 ◽  
Vol 93 (3) ◽  
pp. 166S-167
Author(s):  
M. Friedman ◽  
L. A. Dailey ◽  
D. R. Clemmons
1981 ◽  
Vol 90 (2) ◽  
pp. 372-379 ◽  
Author(s):  
JJ Castellot ◽  
ML Addonizio ◽  
R Rosenberg ◽  
MJ Karnovsky

Using cultured cells from bovine and rat aortas, we have examined the possibility that endothelial cells might regulate the growth of vascular smooth muscle cells. Conditioned medium from confluent bovine aortic endothelial cells inhibited the proliferation of growth-arrested smooth muscle cells. Conditioned medium from exponential endothelial cells, and from exponential or confluent smooth muscle cells and fibroblasts, did not inhibit smooth muscle cell growth. Conditioned medium from confluent endothelial cells did not inhibit the growth of endothelial cells or fibroblasts. In addition to the apparent specificity of both the producer and target cell, the inhibitory activity was heat stable and not affected by proteases. It was sensitive flavobacterium heparinase but not to hyaluronidase or chondroitin sulfate ABC lyase. It thus appears to be a heparinlike substance. Two other lines of evidence support this conclusion. First, a crude isolate of glycosaminoglycans (TCA-soluble, ethanol-precipitable material) from endothelial cell-conditioned medium reconstituted in 20 percent serum inhibited smooth muscle cell growth; glycosaminoglycans isolated from unconditioned medium (i.e., 0.4 percent serum) had no effect on smooth muscle cell growth. No inhibition was seen if the glycosaminoglycan preparation was treated with heparinase. Second, exogenous heparin, heparin sulfate, chondroitin sulfate B (dermatan sulfate), chondroitin sulfate ABC, and hyaluronic acid were added to 20 percent serum and tested for their ability to inhibit smooth muscle cell growth. Heparin inhibited growth at concentrations as low as 10 ng/ml. Other glycosaminoglycans had no effect at doses up to 10 μg/ml. Anticoagulant and non- anticoagulant heparin were equally effective at inhibiting smooth muscle cell growth, as they were in vivo following endothelial injury (Clowes and Karnovsk. Nature (Lond.). 265:625-626, 1977; Guyton et al. Circ. Res. 46:625-634, 1980), and in vitro following exposure of smooth muscle cells to platelet extract (Hoover et al. Circ. Res. 47:578-583, 1980). We suggest that vascular endothelial cells may secrete a heparinlike substance in vivo which may regulate the growth of underlying smooth muscle cells.


Metabolism ◽  
2001 ◽  
Vol 50 (8) ◽  
pp. 955-962 ◽  
Author(s):  
Masahiko Igarashi ◽  
Akihiko Hirata ◽  
Hiroshi Yamaguchi ◽  
Hiromi Tsuchiya ◽  
Hiroshi Ohnuma ◽  
...  

1997 ◽  
Vol 6 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Alison T. Stopeck ◽  
Mahmood Vahedian ◽  
Stuart K. Williams

Intimal hyperplasia in blood vessels is primarily caused by the migration and proliferation of vascular smooth muscle cells. Excessive intimal thickening characterizes atherosclerosis as well as bypass graft and angioplasty failures. Endothelial cell-smooth muscle cell interactions and local cytokine production are important regulators of smooth muscle cell growth. Interferon gamma (γ-IFN), a product of T lymphocytes found in atherosclerotic lesions, inhibits smooth muscle cell proliferation in vitro. To determine if local delivery of γ-IFN may be useful in the treatment or prevention of vascular proliferative diseases, we transferred the human γ-IFN gene into endothelial cells isolated from human arteries and microvessels using a retroviral vector. Biologically active γ-IFN was produced and secreted by γ-IFN transduced endothelial cells, but not by control, nontransduced cells, or cells identically transduced with E. coli beta galactosidase (β-gal). To more closely approximate the microenvironment of blood vessels, subconfluent smooth muscle cells were plated in coculture with control, nontransduced endothelial cells, γ-IFN transduced endothelial cells, or β-gal transduced endothelial cells. Smooth muscle cell growth was inhibited 30-70% by coculture with γ-IFN transduced endothelial cells compared to coculture with β-gal transduced or control endothelial cells (p < 0.05). Our results suggest endothelial cells modified to produce γ-IFN may be a useful therapy in proliferative vascular diseases. Copyright © 1997 Elsevier Science Inc.


2004 ◽  
Vol 13 (3) ◽  
pp. 59 ◽  
Author(s):  
Angela M Taylor ◽  
Catherine Hedrick ◽  
Jerry Nadler ◽  
Ross Hanchett ◽  
Coleen McNamara

2001 ◽  
Vol 16 (suppl_1) ◽  
pp. 14-17 ◽  
Author(s):  
Paula Muñiz ◽  
Ana Fortuño ◽  
Guillermo Zalba ◽  
M. Antonia Fortuño ◽  
Javier Díez

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