Multiple growth factors are released from mechanically injured vascular smooth muscle cells. Crowley, Stephen T., Carla J. Ray, Dilsher Nawaz, Richard A. Majack, and Lawrence D. Horwitz. Divisions of Cardiology, Denver VA Medical Center and University of Colorado School of Medicine, and Department of Pediatrics, University of Colorado School of Medicine, Denver, CO.
APStracts 2:0210H, 1995.
Local release of mitogenic and chemotactic signals during angioplasty -induced vascular injury may initiate restenosis. We investigated whether mechanical injury to vascular smooth muscle cells (VSMC) results in the release of biologically active peptide growth factors. Monolayers of bovine SMC cultures were mechanically injured by cell scraping. Conditioned medium (CM) from control and injured SMC cultures was collected and the mitogenic activity measured by 3[H] thymidine incorporation in recipient SMC cultures. Mitogenic activity from injured CM was detected within 15 minutes after injury. When the CM from injured cells was removed 15 minutes after injury and replaced with serum free media, there was no detectabe mitogenic activity in the replacement CM assessed 1-6 days post injury. Suramin, a nonspecific peptide growth factor antagonist, significantly inhibited the mitogenic activity of injured CM. Basic fibroblast growth factor(bFGF), platelet-derived growth factor (PDGF A chain) and epidermal growth factor (EGF) were detected in CM from injured cells by Western blot. The mitogenic activity of injured CM was significantly inhibited with neutralizing antibodies to bFGF(34%), PDGF-AA (32%), PDGF-BB (25%), EGF (25%). A neutralizing antibody to TGF-beta had no effect. In conclusion, bFGF, PDGF and EGF are immediately released from mechanically injured VSMC. VSMC likely contain preformed, biologically active growth factors, that are efficiently released from the cell cytoplasm following mechanical injury. Conditioned medium from injured VSMC is highly mitogenic and this activity is probably due to multiple growth factors interacting synergistically. 

Received 26 October 1994; accepted in final form 11 May 1995.
APS Manuscript Number H949-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 26 May 1995.