The restenosis paradigm revisited: An alternative proposal for cellular mechanisms

Robert S. Schwartz, David Holmes, Eric J. Topol

Research output: Contribution to journalEditorial

508 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1284-1293
Number of pages10
JournalJournal of the American College of Cardiology
Volume20
Issue number5
DOIs
StatePublished - Nov 1 1992

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Wounds and Injuries
Smooth Muscle Myocytes
Thrombosis
Coronary Restenosis
Neointima
Fibrin
Treatment Failure
Angioplasty
Endothelium
Extracellular Matrix
Actins
Swine
Blood Platelets
Erythrocytes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

The restenosis paradigm revisited : An alternative proposal for cellular mechanisms. / Schwartz, Robert S.; Holmes, David; Topol, Eric J.

In: Journal of the American College of Cardiology, Vol. 20, No. 5, 01.11.1992, p. 1284-1293.

Research output: Contribution to journalEditorial

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