title: The molecular bases of restenosis.
abstract: Studies on the fundamental mechanisms of restenosis after arterial intervention have undergone upheaval. The rat carotid artery has provided perhaps the most widely used experimental preparation for the study of the response to acute arterial injury and gave rise to the multiwave model of restenosis. However, simple arterial injury differs substantially from angioplasty to diseased human vessels. The human intimal lesion already contains abundant smooth muscle cells and leukocytes. Therefore, although the rat carotid injury preparation has provided keen insight into the biology of the response to injury, it mimics human restenosis poorly, if at all. The first wave and second wave of the response to arterial injury so well delineated in rats (medial smooth muscle cell proliferation and migration from media into intima) may not apply to clinical angioplasty injury at all. Smooth muscle proliferation, a constant in injury to animal arteries, may be indolent in human restenosis. Accumulation of extracellular matrix probably explains in part the dissociation between intimal thickening and smooth muscle replication. Also, failure to "remodel" outwards to maintain the increased caliber produced by interventional arterial dilatation, may prove more important than intimal thickening in determining ultimate intimal caliber. Despite a rather disappointing decade of translation of laboratory findings to the clinic, some grounds for optimism in approaching the complications of arterial intervention have emerged. Our appreciation for the biological complexities underlying the restenosis problem have increased. In interventional cardiology we can now proceed, more experienced and wiser, to longer range solutions to help our patients based on mechanistic insights.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: P
authors.initials: P
authors.lastname: Libby
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D002339:Carotid Arteries / Q000473:pathology; D002455:Cell Division; D003251:Constriction, Pathologic; D005109:Extracellular Matrix; D006801:Humans; D009131:Muscle, Smooth, Vascular; D016491:Peripheral Vascular Diseases / Q000473:pathology / Q000628:therapy*; D051381:Rats; D012008:Recurrence; D017539:Tunica Intima / Q000473:pathology*