(Stroke. 1999;30:419-426.)
© 1999 American Heart Association, Inc.
Original Contributions |
Gene Transfer of Human Prostacyclin Synthase Prevents Neointimal Formation After Carotid Balloon Injury in Rats
From the Department of Cerebrovascular Surgery (T. Todaka, H.Y., N.H., I.N., T. Tsukahara), Laboratory for Cerebrovascular Disorders (T. Todaka, H.Y.), and Department of Pharmacology (C.Y., S.H., T.H., T. Tanabe), National Cardio-Vascular Center and NCVC Research Institute, and the Institute for Cellular and Molecular Biology (Y.K.) and Department of Geriatric Medicine (R.M., M.A., T.O.), Osaka University Medical School (T. Tanabe), Osaka, Japan.
Correspondence to Hiroji Yanamoto, MD, DMSc, Laboratory for Cerebrovascular Disorders, National Cardio-Vascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan. E-mail yanamoto{at}ri.ncvc.go.jp
Background and Purpose—A disordered proliferative process in the vascular wall is thought to underlie the pathogenesis of restenosis after percutaneous transluminal angioplasty and carotid endarterectomy. A growth inhibitory property of overexpressed prostacyclin (PGI2) synthase (PGIS) was recently implicated in the pathological proliferation of vascular smooth muscle cells (VSMC) in vitro. Here, we investigated the effects of increased PGI2 synthesis on the pathological proliferation of VSMCs.
Methods—The cDNA encoding human PGIS was transfected into
endothelium-denuded rat carotid arteries after
arterial balloon injury with the use of hemagglutinating
virus Japan (HVJ). HVJ liposome vector complex without PGIS cDNA was
used for vehicle control. The level of 6-keto PGF1
, a
stable hydrolyzed metabolite of PGI2, the
histological distribution of the immunoreactivity for
human PGIS and the ratio of neointimal/medial area were
analyzed.
Results—In the analyses of 6-keto
PGF1, the level in the carotid arteries was
significantly elevated 3 days after PGIS expression-vector transfection
compared with that in the arteries after vehicle transfection. Seven
days after human PGIS expression-vector transfection, the PGIS
cDNA–transfected neointimal cells were strongly positive
for human PGIS immunoreactivity in 81% sections examined. Fourteen
days after the injury, the ratio of neointimal/medial area
was 1.2±0.4 in the PGIS expression-vector transfected group, which was
significantly smaller than that of the vehicle control group, 1.7±0.5;
P<0.01.
Conclusions—It was thus demonstrated that the gene transfer of human PGIS expression-vector into rat carotid arteries resulted in the increased production of human PGI2 in the vascular wall, the expression of human PGIS in the developing neointima and significantly inhibited the neointimal formation generated after balloon injury.
Editorial Comment
Department of Internal Medicine, Cardiovascular Division, University of Iowa College of Medicine, Iowa City, Iowa
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