Different Responses of Neointimal Cells to Imatinib Mesylate and Rapamycin Compared with Normal Vascular Smooth Muscle Cells.
- Author:
Yang Jin PARK
;
Sang Il MIN
;
In Mok JUNG
;
Taeseung LEE
;
Jongwon HA
;
Jung Kee CHUNG
;
Sang Joon KIM
;
Seung Kee MIN
- Publication Type:Original Article
- Keywords:
Imatinib;
Sirolimus;
Intimal hyperplasia;
Neointimal cell;
Carotid artery injury
- MeSH:
Animals;
Arteries;
Carotid Arteries;
Carotid Artery Injuries;
Cell Proliferation;
Cell Survival;
Drug Therapy;
Humans;
Hyperplasia;
Male;
Mesylates*;
Muscle, Smooth, Vascular*;
Neointima;
Rats;
Sirolimus*;
Imatinib Mesylate
- From:Vascular Specialist International
2014;30(1):5-10
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: This study was designed to investigate whether vascular smooth muscle cells (VSMC) from the neointima showed any different response to antiproliferative 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.
