[Antisense monocyte chemotactic protein-1 gene inhibits vein graft intimal hyperplasia in rabbits]

Abstract

Objective: To identify the effect of in vivo local expression of recombine antisense MCP-1 gene on the development of vein graft neointima formation.

Methods: Jugular vein-to-artery bypass grafting was performed on 20 New Zealand white rabbits, of which 4 grafts were transferred with LNCX vectors, 6 grafts with antisense MCP-1 (200 micrograms) by cationic liposome, and 4 grafts as controls. Fourteen days after surgery grafts were harvested. The expression of antisense MCP-1 and its effect on MCP-1 in vein grafts were detected by dot blot. Grafts were processed for morphologic evaluation and immunohistochemistry analysis.

Results: Antisense MCP-1 was expressed in local gene delivery group, meanwhile MCP-1 expression in vein grafts was significantly inhibited (test group, 1.227 +/- 0.362; controls, 1.981 +/- 0.394, P < 0.05). Monocytes/macrophages adherence and infiltration were prominently reduced (test group, 24.3% +/- 2.7%; controls, 36.8% +/- 2.8%, P < 0.05), and intimal hyperplasia was markedly reduced [test group, (0.65 +/- 0.08) mm2; controls, 1.27 +/- 0.15) mm2, P < 0.05].

Conclusion: Local expression of antisense MCP-1 in vein graft significantly reduced intimal hyperplasia with inhibition of MCP-1 expression and prevention of monocytes/macrophages infiltration.