Nanoparticle-mediated arresten gene inhibits neointimal formation of vein grafts: an experimental research.

Background: Recently, we established a new rat model of venous arterialization by grafting the jugular vein into carotid arteries. In many respects, the morphological features of this murine vascular graft model resemble those of human venous bypass graft diseases. Using this model, we studied nanoparticles that mediated the arresten gene to inhibit the neointimal formation of vein grafts.

Methods: Thirty healthy Wistar female rats were randomly divided into three groups. Rat models of grafting the jugular vein into carotid arteries were established. Before and after surgery, all rats were subjected to anticoagulant drugs; and these were subcutaneously injected through different reagents after surgery. Group A: subcutaneous injection of nanoparticles to mediate the arresten gene (0.2 mL); group B: subcutaneous injection of blank nanoparticles (0.2 mL); group C: subcutaneous injection of saline (0.2 mL). At two weeks after the operation, veins of the objective blood vessel were obtained. Pathological changes of local vascular tissues and the new intima hyperplasia of experimental vascular segments were observed. Immunohistochemistry was used to observe the expression of MMPs.

Results: (I) After two weeks, pathological intimal hyperplasia reactions were more obvious in groups B and C than in group A (P<0.05). The difference between groups B and C was not statistically significant (P>0.05); (II) the expression of MMP-2 could be observed in different degrees among the three groups. The expression of MMP-2 markedly increased in groups B and C compared to group A (P<0.05), but the difference between these two groups was not statistically significant (P>0.05).

Conclusions: (I) Nanoparticle-mediated arresten genes can reduce intimal hyperplasia in grafts; (II) we have recently shown that this gene reduced intimal hyperplasia, and this reduction is related to the reduced expression of MMP-2. This shows that the arresten gene can inhibit the degradation of the extracellular matrix (ECM).