Vascular smooth muscle cell migration mediated by thrombin and urokinase-
type plasminogen activator receptor.
Noda-Heiny, Hiroko, M. D. and Burton E. Sobel, M. D.
Hiroko Noda-Heiny, M.D., Cardiovascular Division, Box 8086, Washington
University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110,
Phone 314/362-8924, Fax 314/362-8957
APStracts 2:0024C, 1995.
To determine whether thrombin directly modifies mobility of vascular smooth
muscle cells (SMCs), in Transwell systems (modified Boyden chambers) SMC,
were exposed to [alpha]-thrombin. In concentrations as low as 1 NIH U/ml,
thrombin induced migration as well as proliferation of SMCs. Inhibition of
protein synthesis by cycloheximide (2 [mu]g/ml) obviated thrombin's
chemotactic effect. Neither _-thrombin nor D-phenylalanyl-L-prolyl-L-arginine
chloromethyl ketone (PPACK) inactivated [alpha]-thrombin (both used as
controls) exerted a chemotactic effect. Concomitant hirudin or antithrombin
III plus heparin inhibited chemotaxis by thrombin when added up to 2 hours
after addition of thrombin. [alpha]-Thrombin increased SMC synthesis of
urokinase receptor (uPA-R) and its cell surface expression as shown by
metabolic labeling and immunoprecipitation and by flow cytometry. Thus,
[alpha]-thrombin, in concentrations thought to be present in vivo at sites of
vascular injury, can stimulate not only proliferation but also migration of
vascular SMCs through mechanism(s) possibly involving synthesis of uPA-R,
known to influence migration in diverse types of cells. Accordingly, both
proliferation and migration dependent on thrombin may accelerate
atherosclerosis, restenosis, or both after interventions such as angioplasty.
Received 1 June 1994; accepted in final form 8 November 1994
APS Manuscript Number C0297-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1994 The American Physiological Society.
Published in APStracts on 27 February 1995.