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| CYTOSTATIC GENE-THERAPY FOR VASCULAR PROLIFERATIVE DISORDERS WITH A CONSTITUTIVELY ACTIVE FORM OF THE RETINOBLASTOMA GENE-PRODUCT |
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| Author(s): CHANG MW, BARR E, SELTZER J, JIANG YQ, NABEL GJ, NABEL EG, PARMACEK MS, LEIDEN JM |
| Source: SCIENCE Volume: 267 Issue: 5197 Pages: 518-522 Published: JAN 27 1995 |
| Times Cited: 392 References: 57 |
| Abstract: Vascular smooth muscle cell (SMC) proliferation in response to injury is an important etiologic factor in vascular proliferative disorders such as atherosclerosis and restenosis after balloon angioplasty. The retinoblastoma gene product (Rb) is present in the unphosphorylated and active form in quiescent primary arterial SMCs, but is rapidly inactivated by phosphorylation in response to growth factor stimulation in vitro, A replication-defective adenovirus encoding a nonphosphorylatable, constitutively active form of Rb was constructed. Infection of cultured primary rat aortic SMCs with this virus inhibited growth factor-stimulated cell proliferation in vitro. Localized arterial infection with the virus at the time of balloon angioplasty significantly reduced SMC proliferation and neointima formation in both the rat carotid and porcine femoral artery models of restenosis, These results demonstrate the role of Rb in regulating vascular SMC proliferation and suggest a gene therapy approach for vascular proliferative disorders associated with arterial injury. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV CHICAGO, DEPT MED, CHICAGO, IL 60637 USA
2. UNIV CHICAGO, DEPT PATHOL, CHICAGO, IL 60637 USA
3. UNIV MICHIGAN, MED CTR, DEPT MED, ANN ARBOR, MI 48109 USA
4. UNIV MICHIGAN, MED CTR, DEPT BIOL CHEM, ANN ARBOR, MI 48109 USA
5. UNIV MICHIGAN, MED CTR, HOWARD HUGHES MED INST, ANN ARBOR, MI 48109 USA |
| Publisher: AMER ASSOC ADVAN SCIENCE, 1333 H ST NW, WASHINGTON, DC 20005 |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: QD403 |
| ISSN: 0036-8075 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |