PROLIFERATION IN PRIMARY AND RESTENOTIC CORONARY ATHERECTOMY TISSUE -IMPLICATIONS FOR ANTIPROLIFERATIVE THERAPY

On the basis of animal models of arterial injury, smooth muscle cell p roliferation has been posited as a dominant event in restenosis. Unfor tunately, little is known about this proliferation in the human resten otic lesion. The purpose of this study was to determine the extent and time course of proliferation in primary and restenotic coronary ather ectomy-derived tissue. Primary (n=118) and restenotic (n=100) coronary atherectomy specimens were obtained from 211 nonconsecutive patients. Immunocytochemistry for the proliferating cell nuclear antigen (PCNA) was used to gauge proliferation in the atherectomy specimens. The ide ntity of PCNA-positive cells was then determined using immunohistochem ical cell-specific markers. Eighty-two percent of primary specimens an d 74% of restenotic specimens had no evidence of PCNA labeling. The ma jority of the remaining specimens had only a modest number of PCNA-pos itive cells per slide (typically <50 cells per slide). In the restenot ic specimens, PCNA labeling was detected over a wide time interval aft er the initial procedure (eg, 1 to 390 days), with no obvious prolifer ative peak. Cell-specific immunohistochemical markers identified prima ry and restenotic PCNA-positive cells as smooth muscle cells, macropha ges, and endothelial cells. In conclusion, the findings were as follow s: (1) Proliferation in primary and restenotic coronary atherectomy sp ecimens, as indicated by PCNA labeling, occurs infrequently and at low levels. (2) The response to injury in existing animal models of angio plasty may follow a very different course of events from the clinical reality in human atherosclerotic coronary arteries and may help explai n why current approaches to restenosis therapy have been ineffective.