Author + information
- Received December 16, 1991
- Revision received April 27, 1992
- Accepted May 6, 1992
- Published online November 1, 1992.
- ↵∗Address for correspondence: Robert S. Schwarlz, MD, FACC, Division of Cardiovascular Diseases, 200 First Street, SW, Mayo Clinic, Rochester, Minnesota 55905.
Coronary restenosis is a reparative response to arterial injury during angioplasty, and remains a major clinical problem. The reasons for treatment failures likely stem from our incomplete understanding of the cellular mechanisms in restenotic neointinal formation.
Restenosis is thought to result from migration and replication of medial smooth muscle cells to form an obstructive neointima, a concept neither observed nor demonstrated in humans. An alternative hypothesis for restenosis is based on observations in the porcine coronary injury model. In this model, there are three cellular stages in neointimal formation: thrombotic (stage I), cellular recruitment (stage II) and proliferative (stage III). The thrombotic stage occurs early and consists of platelets, fibrin and red blood cells accumulating at the vessel injury site. In the recruitment stage, the mural thrombus itself develops an endothelium, followed by a mononuclear leukocytic infiltrate beginning on the lumen side of the vessel. In the proliferative stage, a “cap” of actin-positive cells forms on the lumen surface and progressively thickens. These cells do not arise from media at the injury site. Extracellular matrix secretion and additional recruitment likely add to neointimal volume during this phase.
Thrombus assumes a major role in restenosis by providing an absorbable matrix into which smooth muscle cells proliferate. Further studies are needed to validate or modify this hypothesis.
☆ This work was supported by a grant from the J. Holden DeHaan Foundation, Irdianapolis. Indiana, and a grant from Medtronic, Inc., Minneapolis, Minnesota.
- Received December 16, 1991.
- Revision received April 27, 1992.
- Accepted May 6, 1992.