期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1998
卷号：95
期号：3
页码：1213-1217
DOI：10.1073/pnas.95.3.1213
语种：English
出版社：The National Academy of Sciences of the United States of America
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 (FasL) 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 FasL (Ad-FasL) 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-FasL 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-FasL. Prior immunization prevented {beta}-galactosidase expression from Ad-{beta}gal, whereas the expression of the FasL transgene was unaffected. When Ad-{beta}gal and Ad-FasL were delivered together to preimmunized animals, T cell infiltration was reduced and {beta}-galactosidase expression was restored. These data demonstrate that Fas ligand gene transfer can effectively inhibit injury-induced vessel lesion formation and can allow adenovirus-harboring cells to evade immune destruction.
