Genetic engineering of vein grafts resistant to atherosclerosis.

Coronary vein graft disease: Pathogenesis and prevention

“…In animal models, locally delivered gene therapy has prevented intimal hyperplasia in models of arterial balloon injury and venous grafts placed in arterial circulation (46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56) (Table 2). …”

Wild-type p53 gene transfer inhibits neointima formation in human saphenous vein by modulation of smooth muscle cell migration and induction of apoptosis

“…6 To date, a number of studies have targeted different mechanisms involved in the progression of vein graft neointimal thickening, [7][8][9][10][11][12][13] and recently, clinical trials have been initiated. 14 Mann et al 10,11 modulated the cell cycle using antisense oligonucleotides targeting proliferating cell nuclear antigen (PCNA) or cell division cycle 2 (cdc 2) kinase, and reduced neointimal hyperplasia 10 through enhanced nitric oxide bioavailabilty and reduced monocyte adhesion and vascular cell adhesion molecule-1 (VCAM-1) expression. 11 Our previous studies in human and pig models of vein graft neointimal thickening have highlighted the potential benefit of matrix metalloproteinase (MMP) inhibition in prevention of vein graft neointimal hyperplasia.…”

The cell cycle: A critical therapeutic target to prevent vascular proliferative disease

“…It may be necessary to target more than one gene. Combination antisense ODNs directed against more than one cell cycle regulatory gene, such as CDK1 with PCNA or CDK1 with cyclin B, were more effective than a single target approach in a rat model of carotid artery injury (177,178) or experimental vein graft models (187).…”