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.

Characterization of the kallikrein-kinin system, metalloproteinases, and their tissue inhibitors in the in-stent restenosis after peripheral percutaneous angioplasty.

BACKGROUND: The kallikrein-kinin system (KKS) has several direct and indirect effects on cells and cellular mediators involved in the inflammatory process. Studies about inflammation on percutaneous transluminal angioplasty with stent (PTA/stent) to treat peripheral arterial disease (PAD) in humans are scarce. The matrix metalloproteinases (MMPs) are calcium-dependent zinc-containing endopeptidases expressed in various cells and tissues such as fibroblasts, inflammatory cells, and, smooth muscle cells. Changes in the extracellular matrix (ECM) take place in the pathogenesis of many cardiovascular pathologies. MMPs and their inhibitors (tissue inhibitors of metalloproteinases [TIMPs]) are crucial in ECM remodeling in both physiologic and pathologic conditions. The aim of this study was to evaluate the role of the KKS and the MMP metabolism, which are important mediators that may contribute to tissue repair, in the process of arterial restenosis due to intimal hyperplasia in the femoropopliteal segment with the aim of developing new interventions. METHODS: Thirty-nine consecutive patients were selected (regardless of ethnic group, age, or sex) for revascularization, who underwent PTA/stent of the femoropopliteal segment. Twenty-five patients with the same clinical characteristics who were scheduled for diagnostic angiography but not subjected to PTA/nitinol stent were also selected. The concentrations in blood 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, which is an electrophoresis technique, and TIMPs were measured by enzyme-linked immunosorbent assay. RESULTS: Among the 31 patients who completed the survey, there were 10 cases of angiographically defined restenosis of >50%, and 21 cases without restenosis. There was an increase in the concentrations of the substrates (high-molecular-weight kininogens and lower molecular weight kininogens) and enzymes (plasma and tissue kallikrein) in patients with restenosis, indicating activation of this inflammatory pathway in these patients. The activity of kininase II was not significantly different between the groups of patients studied. There were no statistical differences between restenosis and no restenosis patients for both MMPs and TIMPs dosage, but there is an upward trend of MMPs in time 6 months in patients with restenosis. CONCLUSIONS: With the aim of identifying factors contributing to restenosis after endovascular intervention, this study showed evidence of high activation of the KKS in the pathologic inflammatory process of PTA/stent restenosis. In the other hand, it could not show participation of metalloproteinase metabolism in PTA/stent restenosis.