[Influence of antisense N-ras 1 gene on smooth muscle cell proliferation after arterial injury].

OBJECTIVES

To develop a new way to prevent the process of restenosis after arterial injury, we transfered the recombinant antisense N-ras 1 gene to the iliac arteries of rabbits after injury and studied the influence of gene therapy with antisense N-ras 1 on the vascular segment.

METHODS

The constructed recombinant antisense N-ras 1 gene to deliver into the iliac arteries of rabbits after injury. The rabbits were randomly divided into gene therapy group, vector group, and sense N-ras 1 control. The segments of treatment rabbits were analysed by angiography of vessels, pathological study, Northern blotting, and Western blotting technique.

RESULTS

The minimum angiographic lumen diameter measured during gene therapy and at follow-up, for the gene therapy group (at 4 weeks) was 0.80 +/- 0.10mm and the vector control 0.35 +/- 0.13mm (P < 0.01). Histologically, the area of neointima measured, for gene the therapy group (at 4 weeks) was 0.43 +/- 0.05mm2, and the vector control group 0.82 +/- 0.03mm2 (P < 0.01). By using Northern blotting and Western blotting technique, we found that cell's ras mRNA of the vessel segments of gene local delivery was significantly lower than that of the control. Cell's p21 was significantly lower than that of the control.

CONCLUSIONS

The antisense N-ras 1 inhibites VSMC proliferation. The result implicates the potential value in future gene therapy of restenosis.