The Role of Interleukins and Inflammatory Markers in the Early Restenosis of Covered Stents in the Femoropopliteal Arterial Segment.

BACKGROUND: The objective of this study was to evaluate the relationship between inflammatory markers, such as interleukin (IL)-1ß, IL-6, IL-8, IL-10, tumor necrosis factor α (TNF-α), transforming growth factor ß (TGF-ß), and highly sensitive C-reactive protein, and the development of arterial restenosis 6 months after femoropopliteal percutaneous transluminal angioplasty (PTA) with covered stent implantation. METHODS: We recruited 27 patients of a tertiary hospital in Brazil who were treated with covered stents for atherosclerotic peripheral arterial disease. Serum samples were collected before stent implantation, then 24 hr later, and 6 months after the procedure. RESULTS: At 6-month follow-up, 4 patients (15%) presented restenosis. IL1- ß, IL-6, IL-8, and TNF-α levels showed a statistically significant reduction after both 24 hr and 6 months compared with pretreatment levels (P < 0.01). There were increased levels of IL-10 and TGF-ß both 24 hr and 6 months after PTA and stenting compared with pretreatment levels (P < 0.01). None of the cytokines studied were correlated with restenosis. CONCLUSIONS: This study demonstrated a significant increase in anti-inflammatory TGF-ß and IL-10 and a decrease in proinflammatory cytokines IL-1ß, IL-6, IL-8, and TNF-α 6 months after the procedure, but no inflammatory marker was independently identified as a risk factor for in-stent restenosis.

The role of the kallikrein-kinin system, matrix metalloproteinases, and tissue inhibitors of metalloproteinases in the early restenosis of covered stents in the femoropopliteal arterial segment.

OBJECTIVE: The purpose of this study was to investigate the roles of the kallikrein-kinin system and matrix metalloproteinases (MMPs) in the development of arterial restenosis attributable to intimal hyperplasia in the femoropopliteal arteries. METHODS: This report describes a single-center prospective study of 27 patients with peripheral artery disease who required percutaneous transluminal angioplasty and stenting of the femoropopliteal segment using covered stent grafts. The blood concentrations of total and kininogen fractions were evaluated using immunoenzymatic methods. Plasma kallikrein was evaluated by the colorimetric method. Tissue kallikrein was evaluated by the spectrophotometric method. The activity of kininase II was measured by fluorometric analysis. Quantification of MMPs was performed by zymography, and tissue inhibitors of metalloproteinases were measured by enzyme-linked immunosorbent assay. RESULTS: Four (15%) of the treated patients developed restenosis at the 6-month follow-up evaluation. These patients had significantly lower levels of high-molecular-weight kininogens (24 hours; P < .05) and low-molecular-weight kininogens (before, P < .05; 24 hours, P < .01; 6 months, P < .05) and lower levels of tissue inhibitor of metalloproteinases-2 (6 months; P < .05) than the patients without restenosis. The activity levels of plasma and tissue kallikrein, kininase II, and MMPs did not differ significantly between the patients with and without restenosis. CONCLUSIONS: This study demonstrates an involvement of the kallikrein-kinin system in in-stent restenosis, although we could not confirm the participation of metalloproteinases in the restenosis process.