Long term inhibition of neointima formation in balloon-injured rat arteries by intraluminal instillation of a matrix-targeted retroviral vector bearing a cytocidal mutant cyclin G1 construct.
Restenosis from neointimal proliferation is a frequent complication of intracoronary stenting and catheter-based revascularization procedures. Currently, there is no known therapeutic strategy that has been sufficiently effective to warrant its widespread use. In the present study, the anti-proliferative properties of a matrix (collagen)-targeted retroviral vector bearing a mutant cyclin G1 (DNT 41-249) construct was evaluated in vitro and in vivo. In controlled one-month efficacy studies, the intraluminal instillation of the mutant cyclin G1 vector significantly inhibited neointima lesion formation in balloon-injured rat arteries without neointimal growth, associated necrosis or intense inflammatory reaction. Taken together, these data extend the potential utility of the matrix-targeted mutant cyclin G1 retroviral vector for management of vascular restenosis.
Xu
F
F
Department of Molecular Pharmacology and Toxicology, University of Southern California, School of Pharmacy, Los Angeles, CA 90089, USA.
Prescott
M F
MF
Liu
P X
PX
Chen
Z H
ZH
Liau
G
G
Gordon
E M
EM
Hall
F L
FL
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000800:Angioplasty, Balloon / Q000009:adverse effects; D000818:Animals; D002339:Carotid Arteries / Q000737:chemistry / Q000473:pathology; D020212:Carotid Artery Injuries / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins / Q000008:administration & dosage* / Q000032:analysis / Q000235:genetics / Q000627:therapeutic use; D016373:DNA, Antisense / Q000235:genetics; D004274:DNA, Recombinant / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009154:Mutation; D051381:Rats; D012190:Retroviridae / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D016896:Treatment Outcome; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
C534702:CCNG1 protein, human; C534703:Ccng1 protein, mouse; C534704:Ccng1 protein, rat; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins; D016373:DNA, Antisense; D004274:DNA, Recombinant