Antisense proliferating cell nuclear antigen oligonucleotides inhibit intimal hyperplasia in a rat carotid artery injury model.
We have used antisense phosphorothioate oligonucleotides to define the role played by proliferating cell nuclear antigen (PCNA) in neointimal accumulation of smooth muscle cells in a rat carotid artery injury model. The short-term extraluminal delivery of 250 nmol of antisense oligonucleotides, but not control oligonucleotides, immediately after arterial injury produces a 77% suppression of PCNA mRNA after 24 h and a 52% decrease in the frequency of medial smooth muscle cells expressing PCNA after 72 h. This reduction in PCNA expression is accompanied by a 59% decrease in the frequency of proliferating medial smooth muscle cells at 3 d as measured by BudR staining and an 80% decrease in neointimal accumulation assessed morphometrically at 2 wk. Thus, the expression of PCNA is required for medial smooth muscle cell growth in vivo and for neointimal formation after arterial injury.
Simons
M
M
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
Edelman
E R
ER
Rosenberg
R D
RD
D000818:Animals; D001483:Base Sequence; D002339:Carotid Arteries / Q000473:pathology; D002455:Cell Division; D002460:Cell Line; D006965:Hyperplasia; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D009687:Nuclear Proteins / Q000032:analysis / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen; D051381:Rats; D017207:Rats, Sprague-Dawley
D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D018809:Proliferating Cell Nuclear Antigen