Edaravone, a radical scavenger, may enhance or produce antiproliferative effects of fluvastatin, amlodipine, ozagrel, GF109203X and Y27632 on cultured basilar artery smooth muscle cells.
Edaravone, a radical scavenger, may enhance or produce antiproliferative effects of fluvastatin, amlodipine, ozagrel, GF109203X and Y27632 on cultured basilar artery smooth muscle cells.
复制标题
Edaravone 是一种自由基清除剂，可增强或产生氟伐他汀、氨氯地平、奥扎格雷、GF109203X 和 Y27632 对培养的基底动脉平滑肌细胞的抗增殖作用。
DOI：
10.1248/bpb.26.1706
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发表时间：
2003
影响因子：
2
通讯作者：
H. Echizen
中科院分区：
文献类型：
--
作者：
Tomoaki Yamaguchi;K. Oishi;M. Uchida;H. Echizen
活性氧（ROS）刺激血管平滑肌细胞的增殖可能在动脉粥样硬化的发病机制中发挥关键作用。为了阐明ROS促进血管动脉粥样硬化的机制，在存在或不存在的情况下，在5% FBS培养基中研究了氟伐他汀、氨氯地平、奥扎格雷（血栓素合成酶抑制剂）、GF109203X（蛋白激酶C抑制剂）和Y27632（ROCK抑制剂）对豚鼠基底动脉平滑肌细胞（GBa-SM3）增殖的影响3天以上。自由基清除剂依达拉奉。通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑(MTT)测试测量培养结束时细胞的活力。结果表明，氟伐他汀和氨氯地平本身分别在 10-100 µM 和 0.1-1 µM 浓度下对 GBa-SM3 细胞具有抗增殖作用。虽然 100 µM 的依达拉奉本身不具有抗增殖作用，但它显着 (p<0.05) 增强了氟伐他汀和氨氯地平的抗增殖作用。此外，奥扎格雷、GF109203X和Y27632本身对细胞生长没有明显影响。然而，100 µM 的依达拉奉与这些药物的共孵育分别对 10-100 µM、1-10 µM 和 0.1-1 µM 的奥扎格雷、GF109203X 和 Y27632 产生显着的抗增殖作用。总之，依达拉奉可能与氟伐他汀、氨氯地平和奥扎格雷在预防血管动脉粥样硬化方面具有临床有益的相互作用。依达拉奉与蛋白激酶 C 和 ROCK 抑制剂之间的相互作用表明，ROS 触发的细胞内信号可能与这些酶相关，从而导致血管动脉粥样硬化，但需要进一步研究来证实。
Proliferation of vascular smooth muscle cells stimulated by reactive oxygen species (ROS) may play a pivotal role in the pathogenesis of atherosclerosis. To clarify mechanisms by which ROS promote vascular atherogenesis, effects of fluvastatin, amlodipine, ozagrel (thromboxane synthetase inhibitor), GF109203X (a protein kinase C inhibitor) and Y27632 (a ROCK inhibitor) on the proliferation of guinea-pig basilar artery smooth muscle cells (GBa-SM3) in a 5% FBS culture medium were studied over 3 d in the presence or absence of a free radical scavenger, edaravone. Viability of cells at the end of incubation was measured by the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test. Results demonstrated that fluvastatin and amlodipine by themselves possess antiproliferative effects on the GBa-SM3 cells at 10-100 microM and 0.1-1 microM, respectively. While edaravone possessed no antiproliferative effect by itself at 100 microM, it significantly (p<0.05) augmented the antiproliferative effects of fluvastatin and amlodipine. In addition, ozagrel, GF109203X and Y27632 possessed no appreciable effects on the cell growth by themselves. However, coincubation of edaravone at 100 microM with these agents elicited significant antiproliferative effects for ozagrel, GF109203X and Y27632 at 10-100 microM, 1-10 microM and 0.1-1 microM, respectively. In conclusion, edaravone may have clinically beneficial interactions with fluvastatin, amlodipine and ozagrel regarding the prevention of vascular atherosclerosis. The interactions between edaravone and the inhibitors of protein kinase C and ROCK were suggestive of possible contributions of ROS-triggered intracellular signals associated with these enzymes to vascular atherogenesis, but further studies are required for confirmation.
动脉粥样硬化形成过程中的平滑肌细胞膜：氨氯地平预防动脉粥样硬化的潜在靶点。
影响因子：
4.8
作者：
Tulenko,TN;Sumner,AE;Chen,M;Huang,Y;Laury-Kleintop,L;Ferdinand,FD
通讯作者：
Ferdinand,FD
影响因子：
2.2
作者：
DENIZOT, F;LANG, R
通讯作者：
LANG, R