Carbon-Coated Stent and the Role of the Kallikrein-Kinin System in Peripheral Angioplasty.

OBJECTIVE: The purpose of this study was to investigate the clinical evolution of patients treated with carbon-coated stent, as well as its patency and the inflammatory response triggered by this process through the quantification of serum elements of the kallikrein-kinin system (KKS). METHODS: This was a single-center prospective study with 27 patients with peripheral artery disease (PAD) who required percutaneous transluminal angioplasty and stenting of the iliacofemoropopliteal segment using carbon-coated stent grafts (carbostents). The blood concentrations of the total and kininogen fractions were evaluated using immunoenzymatic methods. Plasma kallikrein levels were assessed by the colorimetric method and tissue kallikrein levels were evaluated by the spectrophotometric method. The activity of kininase II was measured by -fluorometric analysis. RESULTS: Of the 27 patients who completed the 6 months of the study (11 iliac territory, 16 femoropopliteal territory), only one experienced restenosis (3.7%) (femoropopliteal segment) and no patient had occlusion (96.3% of patency). In 1 year, four patients were lost to follow-up and all 23 patients evaluated maintained stent patency, except for the patient who had restenosis throughout the first 6 months. We report complete (100%) member salvage in 12 months of follow-up. The activity levels of high- and low-molecular-weight kininogens decreased significantly over time (before vs. 24 h, p < 0.01; before vs. 6 months, p < 0.001, and before vs. 24 h, p < 0.01; before vs. 6 months, p < 0.001; 24 h vs. 6 months, p < 0.001, respectively). Patients also had significantly lower levels of plasma and tissue kallikrein (before vs. 24 h, p < 0.001; before vs. 6 months, p < 0.001, and before vs. 24 h, p < 0.01; before vs. 6 months, p < 0.05, respectively). There was a significant increase in the enzymatic activity of kininase II at 24 h and after 6 months compared to the pre-treatment control (p < 0.001). CONCLUSION: Our early experience shows that the use of carbon-coated stents in PAD appears to be safe, with low rates of early restenosis (3.7% in the first 6 months and 5% in the 12 months of follow-up). We concluded that KKS was involved in the inflammatory response caused by the placement of carbon-coated stents.

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.

Interleukins and inflammatory markers in in-stent restenosis after femoral percutaneous transluminal angioplasty.

BACKGROUND: Inflammatory activity may influence results of percutaneous transluminal angioplasty (PTA). The purpose of this study was to evaluate the relationship between (1) proinflammatory markers (interleukin [IL]-6, IL-8, tumor necrosis factor α (TNF-α), and highly sensitive C-reactive protein [CRP]); (2) type 1 T helper cell marker (IL-12); and (3) Type 2 T helper cell marker (transforming growth factor-ß [TGF-ß]) and in-stent restenosis, 6 months after femoral PTA with stent implantation. METHODS: We performed a single-center prospective study with 26 patients with peripheral artery disease requiring PTA and stenting. As control, we studied 26 patients who were submitted to diagnostic angiography. Serum samples were collected before stent implantation, 24 hr and 6 months after the procedure. To detect restenosis, a new angiography was obtained at 6 months. RESULTS: Restenosis was observed in 10 (38.5%) patients who underwent PTA and stenting. There was a trend to increased levels of IL-6, TNF-α, TGF-ß, and IL-12 24 hr after PTA and stenting compared with pretreatment. IL-8 levels showed a statistically significant reduction 24 hours after versus pretreatment (P < 0.05), 6 months vs. pretreatment, and 6 months vs. 24 hr (P < 0.01). There was no statistical difference between cytokine levels when comparing restenosis and no restenosis groups. CRP levels were already high at pretreatment. CONCLUSIONS: No inflammatory marker was independently identified as risk factor for in-stent restenosis, 6 months after femoral PTA with stent implantation. The question that remains is whether acute phase reactants will be clinically useful to predict the individual risk for in-stent restenosis.