Lovastatin Inhibits Gap Junctional Communication in Cultured Aortic Smooth Muscle Cells
Lovastatin Inhibits Gap Junctional Communication in Cultured Aortic Smooth Muscle Cells
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洛伐他汀抑制培养的主动脉平滑肌细胞的间隙连接通讯
DOI：
10.1177/1074248410373750
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发表时间：
2010-07
影响因子：
2.6
通讯作者：
Zheng, Liang-rong
中科院分区：
文献类型：
--
作者：
Zhu, Jian-hua;Wang, Li-hong;Shen, Jing;Hu, Shen-jiang;Zheng, Liang-rong
背景资料：间隙连接作为细胞间通道，允许相邻细胞之间的离子和其他小分子通过，在重要功能中发挥重要作用，包括调节细胞生长、分化和发育。他汀类药物是一种3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂，可抑制平滑肌细胞（SMC）的迁移和增殖，具有抗增殖作用。最近的研究表明，他汀类药物可以降低间隙连接蛋白连接蛋白43（Cx43）的表达在体内和体外。然而，他汀类药物对间隙连接细胞间通讯（GJIC）的影响的研究很少。本研究假设洛伐他汀通过抑制GJIC抑制血管平滑肌细胞（VSMCs）迁移。方法：用洛伐他汀处理大鼠主动脉平滑肌细胞（RASMCs）。然后用Transwell迁移试验评估血管平滑肌细胞迁移。利用激光扫描共聚焦显微镜进行光漂白后荧光恢复（FRAP）分析，确定间隙连接细胞间通讯。结果：体外培养的RASMCs可通过Transwell系统检测到细胞的迁移。洛伐他汀剂量依赖性地抑制细胞迁移。与对照组（110 ± 26）个相比，0.4、2和10 μ mol/L浓度组迁移的SMC数分别为72 ± 24（P <0.05）、62 ± 18（P <0.01）和58 ± 19（P <0.01）。采用光漂白后5分钟的荧光恢复率（R）作为GJIC的功能指标。10 μ mol/L的洛伐他汀作用48 h后，RASMCs的GJIC的R值为24.38% ± 4.84%，而对照组的R值为36.11% ± 10.53%，表明洛伐他汀对RASMCs的GJIC有明显的抑制作用（P <0.01）。0.08 μ mol/L的洛伐他汀对缝隙连接偶联无明显影响（P > 0.05）。结论：这些结果表明，洛伐他汀通过减弱JIC以剂量依赖的方式抑制迁移。缝隙连接功能的抑制可以增加他汀类药物诱导的抗增殖作用的另一种解释。
Background: Gap junctions, which serve as intercellular channels that allow the passage of ions and other small molecules between neighboring cells, play an important role in vital functions, including the regulation of cell growth, differentiation, and development. Statins, the 3-hydroxy-3-methylglutaryl-coenzymeA (HMG-CoA) reductase inhibitors, have been shown to inhibit the migration and proliferation of smooth muscle cells (SMCs) leading to an antiproliferative effect. Recent studies have shown that statins can reduce gap junction protein connexin43 (Cx43) expression both in vivo and in vitro. However, little work has been done on the effects of statins on gap junctional intercellular communication (GJIC). We hypothesized in this study that lovastatin inhibits vascular smooth muscle cells (VSMCs) migration through the inhibition of the GJIC. Methods: Rat aortic SMCs (RASMCs) were exposed to lovastatin. Vascular smooth muscle cells migration was then assessed with a Transwell migration assay. Gap junctional intercellular communication was determined by using fluorescence recovery after photobleaching (FRAP) analysis, which was performed with a laser-scanning confocal microscope. Results: The migration of the cultured RASMCs were detected by Transwell system. Cell migration was dose-dependently inhibited with lovastatin. Compared with that in the control (110 ± 26), the number of migrated SMCs was significantly reduced to 72 ± 24 (P < .05), 62 ± 18 (P < .01), and 58 ± 19 (P < .01) at the concentration of 0.4, 2, and 10 umol/L, per field. The rate of fluorescence recovery (R) at 5 minutes after photobleaching was adopted as the functional index of GJIC. The R- value of cells exposed to lovastatin 10 umol/L for 48 hours was 24.38% ± 4.84%, whereas the cells in the control group had an R- value of 36.11% ± 10.53%, demonstrating that the GJIC of RASMCs was significantly inhibited by lovastatin (P < .01). Smaller concentrations of lovastatin 0.08 umol/L did not change gap junction coupling (P > .05). Conclusions: These results suggest that lovastatin inhibits migration in a dose-dependent manner by attenuating JIC. Suppression of gap junction function could add another explanation of statin-induced antiproliferative effect.
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影响因子：
1.9
作者：
Q. Zeng;X. Ke;Xiangwei Gao;Yi-ti Fu;D. Lu;H. Chiang;Zheng-ping Xu
通讯作者：
Q. Zeng;X. Ke;Xiangwei Gao;Yi-ti Fu;D. Lu;H. Chiang;Zheng-ping Xu
影响因子：
4.4
作者：
Morimoto, Konosuke;Janssen, William J.;Vandivier, R. William
通讯作者：
Vandivier, R. William
DOI：
10.1046/j.1540-8167.2004.03280.x
发表时间：
2004-02-01
影响因子：
2.7
作者：
Kanagaratnam, P;Cherian, A;Peters, NS
通讯作者：
Peters, NS
影响因子：
15.9
作者：
DUBEY, RK;JACKSON, EK;LUSCHER, TF
通讯作者：
LUSCHER, TF
DOI：
10.1161/01.atv.18.11.1671
发表时间：
1998-11-01
影响因子：
8.7
作者：
Bellosta, S;Via, D;Bernini, F
通讯作者：
Bernini, F