Histopathological Characteristics of Human Coronary Stent Restenosis

Chung, Ick Mo; Cho, Seung Yun

Abstract

BACKGROUND AND OBJECTIVES: Neointimal ingrowth rather than stent recoil is thought to be important for coronary in-stent restenosis. However only limited pathologic data are available to adress the mechanisms of in-stent restenosis. With the specific aim of measuring cell replication and of assessing cellularity and extracellular matrix (ECM) composition, we analyzed atherectomized coronary arterial in-stent restenotic specimens.
METHODS AND RESULTS
In the present study, we analyzed 29 atherectomized coronary arterial in-stent restenotic tissue samples (14 LAD, 10 RCA, and 5 LCX) retrieved from 25 patients (m/f:18/7: age 59+/-13 yr) at 0.5-23 (mean 5.7) months after deployment of Palmaz-Schatz stent. Histopathological analysis of cellular components and ECM was performed using H & E, modified Movat pentachrome, and immunocytochemical staining. Cellular proliferation rate, as estimated by use of antibodies to Ki-67 nuclear antigen showed low proliferation rate with the range of 0-4%, and no positive cells were found in 62% of cases. Myxoid tissue having ECM enriched with versican and hyaluronan was found in 69% of cases, and decreased over time after stenting. Foci of cell poor area were found in 57% of cases, and could be classified into as: (1) containing collagen-rich ECM and (2) containing a proteoglycan-rich ECM. Versican, biglycan, perlecan, and hyaluronan were identified with varying individual distributions in the proteoglycan rich area. Specimens with foci of cell poor area tended to increase over time after stenting (31% in & 4 mo vs. 81% in > or =4 mo after stenting, p<0.01). alpha-smooth muscle actin staining identified the majority of cells as smooth muscle cells (SMC) and occasional macrophages (< or =12 cells per section) were detected by CD68 antibody.
CONCLUSIONS
These data suggest that enhanced ECM accumulation rather than cell proliferation may be important mechanisms for stent restenosis. Angioplasty of stent restenosis may therefore fail due to transient compression of this hygroscopic matrix.