PRECONDITIONING OF SMOOTH-MUSCLE CELLS VIA INDUCTION OF THE HEAT-SHOCK RESPONSE LIMITS PROLIFERATION FOLLOWING MECHANICAL INJURY

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.