Fas ligand gene transfer to the vessel wall inhibits neointima formation and overrides the adenovirus-mediated T cell response

被引:123
作者
Sata, M
Perlman, H
Muruve, DA
Silver, M
Ikebe, M
Libermann, TA
Oettgen, P
Walsh, K
机构
[1] Tufts Univ, Div Cardiovasc Res, St Elizabeths Med Ctr, Sch Med, Boston, MA 02135 USA
[2] Univ Massachusetts, Med Ctr, Dept Physiol, Worcester, MA 01655 USA
[3] Tufts Univ, Sackler Sch Biomed Sci, Program Cell Mol & Dev Biol, Boston, MA 02111 USA
[4] Beth Israel Deaconess Med Ctr, Dept Med, New England Baptist Bone & Joint Inst, Boston, MA 02215 USA
关键词
D O I
10.1073/pnas.95.3.1213
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Proliferation of vascular smooth muscle cells (VSMCs) in response to injury plays a key role in the pathogenesis of vascular disorders, Fas ligand (Fast) induces apoptosis in Fas-bearing cells, and its expression on activated T cells contributes to the regulation of the immune response and physiological cell turnover, Here, we show that a replication-defective adenovirus encoding Fast (Ad-Fast) induced apoptosis in Fas-bearing VSMCs. When introduced locally to balloon-injured rat carotid arteries, a well characterized model of a VSMC-derived lesion, Ad-Fast functioned as a potent inhibitor of neointima formation, In rats immunized with an empty adenoviral vector, robust T cell infiltration of the vessel wall was detected after local delivery of a beta-galactosidase-expressing virus (Ad-beta gal), whereas T cell infiltrates were not detected after local delivery of Ad-Fast, Prior immunization prevented beta-galactosidase expression from Ad-beta gal, whereas the expression of the Fast transgene was unaffected, When Ad-beta gal and Ad-Fast were delivered together to preimmunized animals, T cell infiltration was reduced and beta-galactosidase expression was restored, These data demonstrate that Pas ligand gene transfer can effectively inhibit injury-induced vessel lesion formation and can allow adenovirus-harboring cells to evade immune destruction.
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收藏
页码:1213 / 1217
页数:5
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