Systemic application of anti-ICAM-1 monoclonal antibodies to prevent restenosis in rabbits: an anti-inflammatory strategy.
OBJECTIVE
After vascular intervention, cell adhesion molecules such as ICAM-1 and VCAM are fundamental in inflammatory processes. In particular, ICAM-1 expression is strongly associated with macrophage-rich areas in restenotic lesions. Therefore, we hypothesized an anti-restenotic effect by systemic application of anti-ICAM-1 monoclonal antibodies (mAb).


METHODS
Thirty two rabbits underwent balloon angioplasty and stent implantation either in the right or left iliac artery, Animals received either anti-ICAM mAb or saline solution as a control. Animals were sacrificed 7 (n=8) and 14 (n=8) days and tissue was analyzed for basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGF-beta) expression. Sixteen animals were sacrificed 6 months following treatment and tissue was harvested for histomorphometric analysis.


RESULTS
After balloon injury, bFGF significantly increased from 7 to 14 days only in the control group and was significantly higher compared to the anti-ICAM group. At 14 days after stent implantation, controls showed a significant increase of both bFGF and TGF-beta, whereas the anti-ICAM group only showed a significant increase of TGF-beta. Histomorphometric analysis for neointimal growth did not show any differences between control and anti-ICAM groups either after balloon injury or after stent implantation at 6 months.


CONCLUSIONS
Administration of anti-ICAM-1 mAb following either balloon angioplasty or stent implantation results in a suppression of bFGF in the early phase of restenosis, whereas TGF-beta significantly increases from 7 to 14 days after stent implantation independent of anti-ICAM-1 mAb application. Therefore we conclude that anti-inflammatory strategies are able to interfere with growth factor expression after vascular injury.
Kollum
Marc
M
Department of Cardiology and Angiology, University Clinic of Freiburg, Freiburg i. Br., Germany. marc.kollum@uniklinik-freiburg.de
Hoefer
Imo
I
Schreiber
Ralf
R
Bode
Christoph
C
Hehrlein
Christoph
C
D000800:Angioplasty, Balloon; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use; D023903:Coronary Restenosis / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D007083:Iliac Artery / Q000473:pathology; D007118:Immunoassay; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000627:therapeutic use; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D011817:Rabbits; D015607:Stents
D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D018799:Intercellular Adhesion Molecule-1