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[Artery denuded model and effects of three kinds of antisense c-myc RNA]
Objective:
To investigate the effects of antisense c-myc on injured vascular wall.
Methods:
Three recombinant retroviral expression vectors, aM1, aM2 and aM3, which loading the reverse fragment of exon1, 2 and 3 respectively, were transferred into denuded rabbit femoral artery wall and were assayed 21 days after operation.
Results:
(1) The regions of rabbit femoral artery were not only convenient for injury control, drug giving and material drawing, but also gave a neointimal area to media area vatio of 1.37:1. Their intensity and area of c-myc expression in media increased to 1.8 and 1.5 fold of normal value. (2) c-myc expression in aM2, aM3 and aM1 was reduced by 37.5%, 20.8%, and 17.8% with media intensity, 71.5%, 57.2%, and 61.6% with media area and 31.3%, 20.8%, and 17.8% with neointimal intensity respectively. (3) Neointimal area/media area of aM2 group reduced by 72.6%, aM3 group reduced by 35.2%, aM1 group had no significant difference comparing with control group. (4) Proliferating cellular nuclear antigen (PCNA) in the intimal and media of the three antisense transferred groups was enhanced with their expressive intensities, but reduced with expressive areas significantly. (5) With the declining of neointimal area/media area, alpha-SM actin expression in the intimal and media of the three antisense transferred groups was significantly increased (aM2 > aM3 > aM1).
Conclusion:
(1) Rabbit femoral artery denuded model is a satisfactory animal model. (2) Antisense c-myc transferring can reduce or resist the c-myc increase in injured artery wall, resist neointimal hyperplasia and smooth muscle cells dedifferentiation,especially c-myc exon 2 antisense RNA vector aM2.
Insights
Antisense c-myc therapy effectively reduces neointimal hyperplasia in injured rabbit arteries. The c-myc exon 2 antisense RNA vector (aM2) demonstrated the most significant reduction in neointimal hyperplasia and smooth muscle cell dedifferentiation.
Area of Science:
- Vascular Biology
- Molecular Medicine
- Gene Therapy
Context:
- Vascular injury triggers cellular proliferation, leading to neointimal hyperplasia.
- The c-myc oncogene plays a critical role in vascular smooth muscle cell proliferation and differentiation.
Purpose:
- To investigate the therapeutic potential of antisense c-myc in mitigating neointimal hyperplasia following vascular injury.
- To evaluate the efficacy of different antisense c-myc exon vectors in a rabbit femoral artery denudation model.
Summary:
- Three antisense c-myc retroviral vectors (aM1, aM2, aM3) were introduced into injured rabbit femoral arteries.
- Antisense c-myc significantly reduced neointimal area, suppressed c-myc expression, and inhibited smooth muscle cell dedifferentiation, with aM2 showing the greatest effect.
- PCNA and alpha-SM actin expression patterns indicated reduced proliferation and enhanced differentiation in antisense-treated groups.
Impact:
- The rabbit femoral artery denudation model is validated as suitable for studying vascular injury responses.
- Antisense c-myc gene therapy presents a promising strategy to prevent or treat neointimal hyperplasia and associated vascular remodeling.