Figure 8-1: Catheters for cardiovascular gene therapy. (From Nabel,95 with permission.) Figure 8-2: Principal of E2F "decoy" strategy. TTTCGCGC is the consensus sequence for the E2F binding site. In the quiescent cell state, the transcription factor E2F is complexed with Rb (retinoblastoma gene product), cyclin A, and the cyclin-dependent kinase cdk2 (top). Phosphorylation of Rb releases free E2F, which binds to cis elements of the cell cycle regulatory genes, resulting in the transactivation of these genes (middle). The E2F decoy cis-element double-stranded oligonucleotide binds to free E2F, preventing E2F-mediated transactivation of cell cycle regulatory genes (bottom). (From Morishita et al.,45 with permission.)

Figure 8-3: Control oligonucleotide-treated (A and B) and ASO (against cdc2 kinase/PCNA)-treated vein grafts (C and D) in hypercholesterolemic rabbits 6 weeks after surgery (x70). Sections of 5 mm were stained with hematoxylin/van Gieson (A and C) and a monoclonal antibody against rabbit macrophages (B and D). Arrows indicate the location of the internal elastic lamina. (From Mann et al.,63 with permission.) Figure 8-4: Regulation of the cell cycle. Progression through the G1 phase of the cell cycle is regulated by the assembly and phosphorylation of cyclins and cyclin-dependent kinases (CDKs). The cyclin-CDK complexes are inhibited by cyclin-dependent kinase inhibitors (CKIs), of which p21 and p27 are examples. These CKIs lead to G1 arrest. Inhibition of Rb phosphorylation, inactiviation of E2F, or inhibition of cyclin A and B also lead to disruption of DNA synthesis and inhibition of cell proliferation. (From Tanner et al.,96 with permission.)

Figure 8-5: Inhibition of neointimal hyperplasia by in vivo gene transfer of endothelial cell nitric oxide synthase (ecNOS) in balloon-injured rat carotid arteries. A. Normal artery. B. Injured, untransfected artery. C. Injured, control vector-transfected artery. D. Injured, ecNOS-transfected artery. M, media; N, neointima. (From von der Leyen et al.,80 with permission.)


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