Histopathological Characteristics of Human Coronary Stent Restenosis

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.

A Histopathologic Analysis of Atherectomized Human Coronary Stent Restenosis :Potential Role of Cell Migration and Extracellular Matrix Formation

BACKGROUND: Neointimal ingrowth rather than stent recoil has thought to be important for coronary arterial in-stent restenosis. Intuitively cell migration and extracellular matrix (ECM) formation seems to be important in the pathogenesis of stent restenosis. Therefore, with specific aim of identifying molecules implicated in cell migration and extracellular matrix formation, histopathologic analysis on atherectomized coronary arterial in-stent restenotic tissue was performed. METHODS: In the present study we analyzed 29 atherectomized coronary arterial in-stent restenotic tissue specimens (LAD 14, LCX 5, RCA 10) retrieved (5.7+/-5.4 months after stent deployment) from 25 patients (age 59+/-13, M/F:18/70) in whom restenosis complicated previous revascularization with Palmaz-Schatz stent. Histopathologic analysis was performed after immunostaining. Antibodies against TGF- 1, hyaluronan synthase (HAS) 1, MMP1, MMP9, urokinase type plasminogen activator, PDGF receptor were used for immunostaining. RESULTS: Myxoid tissue characterized by stellate-shaped cells embedded in a loose ECM was present in 20 out of 29 specimens, and tends to decrease over time after stenting. Foci of cell poor area (48-320 cells/mm2) in a microscopic field was present in 17 out of 29 specimens, and tends to increase over time after stenting (13/16 in or =4 mo, p<0.01). Various proportions of specimens show positive stained cells with respect to each antibodies: TGF 1 in 16 out of 20:HAS1 in 10 out of 13:MMP1 in 8 out of 16:MMP9 in 4 out of 13:PDGF receptor in 12 out of 17 specimens. Abundant cells labled with certain antibodies (TGF 1, uPA, PDGF receptor) were frequently found in myxoid tissue. CONCLUSIONS: Myxoid tissue, frequently found in stent restenotic tissue, may be a biologically active tissue in terms of cell migration and of ECM formation. ECM accumulation tends to increase over time after stenting and may be important in pathogenesis of coronary arterial stent restenosis.