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Different Responses of Neointimal Cells to Imatinib Mesylate and Rapamycin Compared with Normal Vascular Smooth
Yang Jin Park1, Sang-Il Min2, In Mok Jung2
1Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul.
Purpose:
This study was designed to investigate whether vascular smooth muscle cells (VSMC) from the neointima showed any different response to anti-proliferative agents, such as rapamycin or imatinib mesylate, compared to VSMCs from normal artery.
Materials And Methods:
Intimal hyperplasia was made by carotid balloon in jury in male rats. Neointimal cells at 4 weeks after injury and normal VSMCs were extracted by enzymatic isolation method and cultured. Cell viability and proliferation were tested in VSMCs from injured left carotid artery and uninjured right carotid artery. Tests were repeated with rapamycin, imatinib mesylate or both in various concentrations.
Results:
Rapamycin decreased cell viability only at a high concentration of 10(-5) M in uninjured VSMCs. Combined drugs decreased cell viability at a lower concentration of 10(-7) M in uninjured VSMCs, and at a higher concentration of 10(-5) M in neointimal cells. Overall, rapamycin showed cytocidal effects at a high concentration of 10(-5) M, whereas imatinib did not. Cell proliferation of neointima was significantly decreased along with the drug concentration. Cell proliferation of uninjured VSMCs was significantly decreased at higher drug concentrations. Combined drug therapy showed synergistic effects. Overall, neointimal cells are more susceptible to the antiproliferative effects of the drugs.
Conclusion:
Neointimal cells from the injured carotid artery are more susceptible to the antiproliferative effect of imatinib and rapamycin. Both drugs can be a used for the prevention of intimal hyperplasia, which could be investigated through further in vivo studies.
Insights
Vascular smooth muscle cells (VSMCs) from injured arteries are more sensitive to anti-proliferative drugs like rapamycin and imatinib. This suggests potential for preventing intimal hyperplasia with these agents.
Area of Science:
- Vascular Biology
- Pharmacology
Background:
- Intimal hyperplasia is a significant factor in vascular graft failure and restenosis.
- Vascular smooth muscle cells (VSMCs) play a critical role in the development of intimal hyperplasia.
Purpose of the Study:
- To compare the response of VSMCs from neointima versus normal arteries to anti-proliferative agents.
- To investigate the efficacy of rapamycin and imatinib mesylate on VSMC viability and proliferation.
Main Methods:
- Rat carotid artery balloon injury model to induce neointimal hyperplasia.
- Enzymatic isolation and culture of neointimal VSMCs and normal VSMCs.
- Assessment of cell viability and proliferation in response to varying concentrations of rapamycin, imatinib mesylate, and combination therapy.
Main Results:
- Neointimal VSMCs demonstrated increased susceptibility to the antiproliferative effects of both rapamycin and imatinib mesylate compared to normal VSMCs.
- Combined drug therapy exhibited synergistic antiproliferative effects at lower concentrations.
- Rapamycin showed cytocidal effects at high concentrations, while imatinib did not.
Conclusions:
- Neointimal VSMCs are more sensitive to the antiproliferative actions of imatinib and rapamycin.
- These drugs hold promise for the prevention of intimal hyperplasia, warranting further in vivo investigation.
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