Inhibition of restenosis formation without compromising reendothelialization as a potential solution to thrombosis following angioplasty?
Stent thrombosis remains an important problem after the implantation of different stent types. A potential solution to this problem may be vasoactive agents with dual effects on different cell types like C-type natriuretic peptide (CNP). Therefore, in vitro and in vivo effects of CNP were investigated in a porcine restenotic model. Gene transfer of CNP in cultures of porcine vascular cells revealed up to 30% reduction of growth of smooth muscle cells (p<.05), but no suppression of endothelial growth using CNP. Applied in vivo, angiography revealed a trend of reduced restenosis formation in balloon-injured porcine arteries treated with CNP gene or beta-galactosidase (beta-Gal) control gene after three months (2.59 +/- 2.04-fold reduction, p = n.s.). Histologically, morphometry revealed significantly reduced neointima formation after treatment with CNP plasmid (7.26 +/- 1.44-fold reduction, p < .05). Evans blue staining demonstrated complete endothelial repair already 3 weeks after intervention using CNP. Transfer of CNP gene resulted in a significant inhibition of neointima formation without compromising endothelial repair. Therefore, use of the CNP gene may offer a solution to suppress restenosis formation while preventing subacute or late thrombosis.
Department of Paediatric Cardiology, University Hospital Grosshadern, Ludwig Maximilian University, Munich, Germany.
Alexandra Theresia
AT
Fuchs
Andreas
A
Kuehnl
Jaroslav
J
Pelisek
Pierre Henri
PH
Rolland
Choukri
C
Mekkaoui
Heinrich
H
Netz
Sigrid
S
Nikol
D000792:Angiography; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D001158:Arteries / Q000166:cytology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004396:Coloring Agents / Q000378:metabolism; D003251:Constriction, Pathologic; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D004730:Endothelium, Vascular / Q000503:physiopathology; D005070:Evans Blue / Q000378:metabolism; D015870:Gene Expression; D018014:Gene Transfer Techniques; D007150:Immunohistochemistry; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D020098:Natriuretic Peptide, C-Type / Q000008:administration & dosage* / Q000235:genetics*; D013552:Swine; D013927:Thrombosis / Q000517:prevention & control*; D013997:Time Factors; D014162:Transfection; D017539:Tunica Intima / Q000187:drug effects
D004396:Coloring Agents; D020098:Natriuretic Peptide, C-Type; D005070:Evans Blue; D004247:DNA