Mj. Slepian et al., PRECONDITIONING OF SMOOTH-MUSCLE CELLS VIA INDUCTION OF THE HEAT-SHOCK RESPONSE LIMITS PROLIFERATION FOLLOWING MECHANICAL INJURY, Biochemical and biophysical research communications, 225(2), 1996, pp. 600-607
Arterial smooth muscle cell (SMC) proliferation is a significant compo
nent of post-angioplasty restenosis. We evaluated whether pre-conditio
ning of SMCs, via induction of the heat shuck respone prior to actual
physical injury, would result in an alteration in cell proliferation f
ollowing injury. Rat aortic SMCs were pretreated with either chemical
or thermal heat shock inducers and then subjected to scrape-wound inju
ry in vitro. Cell proliferation at 24 hrs was measured via H-3-thymidi
ne (Tdr) incorporation and compared with scrape wounded unstressed con
trols. A significant decline in cell proliferation post scrape-wound i
njury was observed for both chemical and thermal heat shock pre-condit
ioned cultures, compared to untreated controls. Increased expression o
f heat shock protein 72 was confirmed serially throughout the 24 hr st
udy period for both chemical and thermal inducers. Despite reduced pro
liferation heat shocked cells remained viable as evidenced by fluoresc
ent cell viability assay and preserved migration. Pre-conditioning of
SMCs through induction of the heal shock response prior to physical in
jury may be a useful approach to limit aggressive proliferation observ
ed with mechanical revascularization injury. (C) 1996 Academic Press,
Inc.