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

ABSTRACT

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/F18/70) 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 20HAS1 in 10 out of 13MMP1 in 8 out of 16MMP9 in 4 out of 13PDGF 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.