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.
Division of Vascular and Endovascular Surgery, Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. Electronic address: lauravascular@gmail.com.
Laura Andrade
LA
Rocha
Division of Vascular and Endovascular Surgery, Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Carlos Eli
CE
Piccinato
Division of Vascular and Endovascular Surgery, Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Mauricio Serra
MS
Ribiero
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Christiane
C
Becari
Division of Vascular and Endovascular Surgery, Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Renata Dellalibera
RD
Joviliano
Division of Vascular and Endovascular Surgery, Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Edwaldo Edner
EE
Joviliano
D000328:Adult; D000368:Aged; D000800:Angioplasty, Balloon / Q000009:adverse effects / Q000295:instrumentation*; D015415:Biomarkers / Q000097:blood; D001938:Brazil; D003251:Constriction, Pathologic; D005260:Female; D005263:Femoral Artery; D006801:Humans; D006965:Hyperplasia; D007610:Kallikreins / Q000097:blood*; D019679:Kininogen, High-Molecular-Weight / Q000097:blood*; D019728:Kininogen, Low-Molecular-Weight / Q000097:blood*; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood*; D008875:Middle Aged; D058426:Neointima; D058729:Peripheral Arterial Disease / Q000097:blood / Q000175:diagnosis / Q000201:enzymology / Q000628:therapy*; D011150:Popliteal Artery; D011446:Prospective Studies; D011474:Prosthesis Design; D012008:Recurrence; D015607:Stents; D013997:Time Factors; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood*; D016896:Treatment Outcome
D015415:Biomarkers; D019679:Kininogen, High-Molecular-Weight; D019728:Kininogen, Low-Molecular-Weight; D019714:Tissue Inhibitor of Metalloproteinases; D007610:Kallikreins; D020782:Matrix Metalloproteinases