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Recombinant adeno-associated viral vector encoding human VEGF165 induces neomicrovessel formation in the adult mouse brain

2006; Frontiers in Bioscience; Volume: 11; Issue: 1 Linguagem: Inglês

10.2741/2042

1094-3935

Fanxia Shen,

interferon and immune responses

Delivery of therapeutic genes represents a fascinating possibility to accelerate the injury-repairing process in tissues that are otherwise difficult to treat, such as cerebral ischemia. Current studies indicate that gene transfer-induced focal angiogenesis in the brain may provide an important therapeutic strategy. In the present study, we report the efficacy of induction of angiogenesis with an adeno-associated virus (AAV) vector expressing the 165 amino acid isoform of vascular endothelial growth factor (VEGF165). We found that AAV serotype 1 had more efficiency in transduction of the brain tissue than AAV serotype 2. Quantitative vessel counting showed that microvessels in AAV-VEGF-transduced mice significantly increased from 1 to 12 weeks compared to the control groups (AAV-VEGF: 316±58 vs. AAV-lacZ: 180±34 and saline: 152±35 vessels/mm2, at 6 weeks, p<0.05). Proliferating cell nuclear antigen (PCNA) staining confirmed these microvessels were actively proliferating. Double-labeled fluorescence staining demonstrated that neurons, astrocytes, and endothelial cells could express VEGF following AAV-VEGF gene transfer. AAV vectors did not elicit a detectable inflammatory response, cell loss or neuronal damage. Our data underline the importance of angiogenesis in the brain tissue and indicate that VEGF gene transfer may present a valuable approach to treat brain ischemic disorders.