Gene transfer of vascular endothelial growth factor and endothelial nitric oxide synthase--implications for gene therapy in cardiovascular diseases.

Gene therapy is based on the delivery of exogenous genetic material in order to influence the endogenous genetic components involved in disease development. This new therapeutic approach has been suggested to have great potential in the treatment of insufficient angiogenesis or in prevention of restenosis after balloon angioplasty of atherosclerotic arteries. As both vascular endothelial growth factor (VEGF) and nitric oxide (NO) exert beneficial effects on vascular physiology, we studied the generation of both compounds after in vitro transfection of relevant genes. The plasmid vectors, containing VEGF cDNA were constructed and lipotransfected into vascular smooth muscle cells (VSMC). Transfected cells generated up to a few nanograms of VEGF, which induced proliferation of endothelial cells. VSMC transfected with another plasmid, containing endothelial constitutive NO synthase (ecNOS) cDNA generated micromolar quantities of nitrite. Moreover, such NO-producing cells synthesized significantly more VEGF than VSMC transfected with control plasmids. Thus, the study demonstrated that transfer of VEGF and/or NOS genes to VSMC led to the production of measurable amounts of both VEGF protein and NO. Additionally, we evidenced that NO can enhance the endogenous generation of VEGF. A new protective mechanism of NO has been thus revealed.