Neointimal growth can be influenced by local adventitial gene manipulation via a needle injection catheter

被引:24
作者
Huehns, TY
Krausz, E
Mrochen, S
Schmid, M
Engelmann, MG
Esin, S
Schrittenloher, PK
Höfling, B
Günzburg, WH
Nikol, S
机构
[1] Univ Munich, Klinikum Grosshadern, Med Clin 1, D-81377 Munich, Germany
[2] GSF Neuherberg, Inst Mol Virol, D-80806 Munich, Germany
[3] Univ Vet Sci, Inst Virol, A-1210 Vienna, Austria
关键词
restenosis; gene transfer; liposomes; pig model; local drug delivery; cell cycle;
D O I
10.1016/S0021-9150(99)00048-9
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Revascularization by percutaneous transluminal coronary angioplasty is limited in the long-term by restenosis, which is luminal renarrowing in the first 6 months after the procedure. Smooth muscle cell proliferation is thought to be an important factor in restenosis; this leads to neointima formation and arterial lumen narrowing. Local therapy delivered perivascularly may have an effect on events in the neointima and reduce restenosis. The effect of delivering expression vector plasmids for senescent cell-derived inhibitor SDI-1, which regulates cell proliferation, and its antisense, into the perivascular tissue of injured arteries was investigated in a porcine arterial injury model using a needle injection catheter. Transfection efficiency, biological effect and plasmid dissemination were evaluated in arterial and organ tissue sections between 2 days and 4 months. A limited number of adventitial, medial and neointimal cells were transfected up to 4 months. sdi gene transfer did not result in a change in neointima. Transfer of antisense sdi resulted in an increase in neointima after 3 weeks. No DNA plasmid was detected in control tissues. Liposomally-mediated adventitial local gene delivery is feasible and safe using the needle injection catheter in a porcine model. A limited number of cells was transfected, with expression of transfected genes up to 4 months after delivery. A transient biological effect with increased neointima was observed after delivery of the antisense sdi gene. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:135 / 150
页数:16
相关论文
共 37 条
[11]   BLOOD-FLOW THROUGH VASA VASORUM OF CORONARY-ARTERIES IN ATHEROSCLEROTIC MONKEYS [J].
HEISTAD, DD ;
ARMSTRONG, ML .
ARTERIOSCLEROSIS, 1986, 6 (03) :326-331
[12]  
Hofling B, 1996, J INVASIVE CARDIOL, V8, P388
[13]  
HOFLING B, 1995, EUR HEART J, V16, P437
[14]   Adventitia as a target for intravascular local drug delivery [J].
Huehns, TY ;
Gonschior, P ;
Hofling, B .
HEART, 1996, 75 (06) :537-538
[15]  
HUPPI K, 1994, ONCOGENE, V9, P3017
[16]  
INNIS MA, 1990, PCR PROTOCOLS GUIDE, P84
[17]  
JIANG HP, 1995, ONCOGENE, V10, P1855
[18]   PERSISTENCE OF PLASMID DNA AND EXPRESSION IN RAT-BRAIN CELLS INVIVO [J].
JIAO, SS ;
ACSADI, G ;
JANI, A ;
FELGNER, PL ;
WOLFF, JA .
EXPERIMENTAL NEUROLOGY, 1992, 115 (03) :400-413
[19]  
MILLER AD, 1989, BIOTECHNIQUES, V7, P980
[20]   Inducible expression of p21(WAF-1/CIP-1/SDI-1) from a promoter conversion retroviral vector [J].
Mrochen, S ;
Klein, D ;
Nikol, S ;
Smith, JR ;
Salmons, B ;
Gunzburg, WH .
JOURNAL OF MOLECULAR MEDICINE-JMM, 1997, 75 (11-12) :820-828