Histopathology of in-stent restenosis in patients with peripheral artery disease.
BACKGROUND
Clinical studies have suggested that smooth muscle cell (SMC) hyperplasia is the most likely cause of in-stent restenosis. However, pathological data regarding this issue are limited. Specifically, direct evidence of proliferative activity in tissues excised from stenotic stents has not been previously reported.


RESULTS
Tissue specimens were retrieved by directional atherectomy from 10 patients in whom in-stent restenosis complicated percutaneous revascularization of peripheral artery disease. Analysis of cellular composition was performed quantitatively after cell-specific immunostaining. For specimens preserved in methanol (7 of 10), cellular proliferation was evaluated by use of antibodies to proliferating cell nuclear antigen (PCNA), cyclin E, and cdk2. TUNEL staining for apoptosis was performed on 8 paraformaldehyde-preserved specimens. Each of the 10 specimens contained extensive foci of hypercellularity composed predominantly of SMCs (mean+/-SEM, 59.3+/-3.0%). Evidence of ongoing proliferative activity was documented in all 7 methanol-preserved specimens: 24.6+/-2.3% of SMCs were PCNA-positive, 24.8+/-3.1% were cyclin E-positive, and 22.5+/-2.2% were cdk2-positive. Apoptotic cells were detected in all 8 specimens that had been appropriately preserved to permit DNA nick-end labeling. Macrophages and leukocytes were identified in each of the 10 specimens but accounted for a proportionately smaller number of cells (14.5+/-1.9% and 9.5+/-1.4%, respectively). Organized thrombus was observed in 6 of the 10 specimens.


CONCLUSIONS
These findings support the notion that in-stent restenosis results from SMC hyperplasia and suggest that adjunctive therapies designed to inhibit SMC proliferation may further enhance the utility of endovascular stents.
Kearney
M
M
Department of Medicine (Cardiology), St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Mass. 02135, USA.
Pieczek
A
A
Haley
L
L
Losordo
D W
DW
Andres
V
V
Schainfeld
R
R
Rosenfield
K
K
Isner
J M
JM
D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D017209:Apoptosis; D001157:Arterial Occlusive Diseases / Q000473:pathology* / Q000601:surgery; D002455:Cell Division; D005260:Female; D006801:Humans; D006965:Hyperplasia; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D016491:Peripheral Vascular Diseases / Q000473:pathology* / Q000601:surgery; D012008:Recurrence; D015607:Stents