Department of Interventional Radiology, The Sixth People's Hospital Affiliated to Shanghai Jiaotong University, No 600 Yishan road, Xuhui District, Shanghai, 200233, China.
Department of Interventional Radiology, The Sixth People's Hospital Affiliated to Shanghai Jiaotong University, No 600 Yishan road, Xuhui District, Shanghai, 200233, China.
Biomed Pharmacother. 2017 Sep;93:180-189. doi: 10.1016/j.biopha.2017.06.027. Epub 2017 Jun 19.
Excessive proliferation and migration of vascular smooth muscle cells(VSMCs) and delayed proliferation and migration of endothelial cells(ECs) were the main cause of restenosis after endovascular interventional therapy. Since tacrolimus has proved to be more sensitive to inhibiting VSMCs' proliferation,and platelet-derived growth factor-BB(PDGF-BB) benefitted ECs' and VSMCs' proliferation, this study was aimed to identify combined effect of tacrolimus and PDGF-BB, investigate any mechanisms underneath and demonstrate combined effect of two drugs in vivo. As the results showed we confirmed differential effect of PDGF-BB and tacrolimus on ECs and VSMCs. On the concentration level of 2-5μg/ml tacrolimus plus 10ng/ml PDGF-BB, combination of drugs could effectively promote ECs proliferation and migration, and meanwhile inhibit VSMCs proliferation and migration, and the inhibition of p-mTOR's expression within VSMCs played an important role in this differentiated effect. Raising concentration level of PDGF-BB would weaken inhibitory effect of tacrolimus on both kinds of cell. For injured intima, the mix solution of two drugs could promote intima healing and suppress excessive intimal hyperplasia.
血管平滑肌细胞（VSMCs）过度增殖和迁移以及内皮细胞（ECs）增殖和迁移延迟是血管内介入治疗后再狭窄的主要原因。由于他克莫司已被证明对抑制 VSMCs 的增殖更敏感，而血小板衍生生长因子-BB（PDGF-BB）有利于 ECs 和 VSMCs 的增殖，因此本研究旨在确定他克莫司和 PDGF-BB 的联合作用，探讨其潜在机制，并在体内证明两种药物的联合作用。结果表明，我们证实了 PDGF-BB 和他克莫司对 ECs 和 VSMCs 的不同作用。在 2-5μg/ml 他克莫司加 10ng/ml PDGF-BB 的浓度水平下，药物联合可有效促进 ECs 的增殖和迁移，同时抑制 VSMCs 的增殖和迁移，VSMCs 中 p-mTOR 的表达抑制在这种分化作用中起重要作用。提高 PDGF-BB 的浓度水平会削弱他克莫司对两种细胞的抑制作用。对于受损的内膜，两种药物的混合溶液可促进内膜愈合并抑制内膜过度增生。
