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KMID : 1037520140300010005
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Vascular Specialist International
2014 Volume.30 No. 1 p.5 ~ p.10
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Different Responses of Neointimal Cells to Imatinib Mesylate and Rapamycin Compared with Normal Vascular Smooth Muscle Cells
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Park Yang-Jin
Min Sang-Il
Jung In-Mok
Lee Tae-Seung
Ha Jong-Won
Chung Jung-Kee
Kim Sang-Joon
Min Seung-Kee
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Abstract
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Purpose: This study was designed to investigate whether vascular smooth mus-cle 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 test ed in VSMCs from injured left carotid artery and uninjured right carotid ar tery. 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 con-centration 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 con-centration 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.
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KEYWORD
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Imatinib, Sirolimus, Intimal hyperplasia, Neointimal cell, Carotid artery injury
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