Dan Juhua, Sun Xin, Li Wanlu, Zhang Yun, Li Xuesong, Xu Haobo, Li Zhitao, Tian Zhen, Guo Shuyuan, Yao Jianting, Gao Weidong, Tian Ye
Department of Pathophysiology, State Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin Medical University, Harbin, China.
Division of Cardiology, First Affiliated Hospital, Harbin Medical University, Harbin, China.
Ultrasound Med Biol. 2015 Jun;41(6):1681-9. doi: 10.1016/j.ultrasmedbio.2014.12.664. Epub 2015 Mar 18.
Sonodynamic therapy (SDT) has been found to inhibit in-stent restenosis in animal models. However, the mechanism is not fully elucidated. Here, we investigated the effects of 5-aminolevulinic acid (ALA)-mediated SDT (ALA-SDT) on vascular smooth muscle cells (VSMCs), a cause of restenosis, with a focus on SDT-induced phenotypic switching. Serum-induced dedifferentiated VSMCs were cultured with ALA (1 mm, 24 h) and exposed to ultrasound (0.8 W/cm(2)) for 5 min. Results indicated that ALA-SDT inhibited the migration and proliferation of VSMCs and enhanced the expression of differentiated phenotypic markers in VSMCs. Additionally, ALA-SDT increased intracellular reactive oxygen species accumulation and phosphorylated p38 mitogen-activated protein kinase in VSMCs. Inhibition of reactive oxygen species elevation or p38 mitogen-activated protein kinase activity abolished the expression of smooth muscle 22α (SM22α) in VSMCs induced by ALA-SDT. Taken together, these results suggest that ALA-SDT promotes transformation of the VSMC phenotype from the dedifferentiated to differentiated status via reactive oxygen species and activated p38 mitogen-activated protein kinase.
声动力疗法（SDT）已被发现在动物模型中可抑制支架内再狭窄。然而，其机制尚未完全阐明。在此，我们研究了5-氨基酮戊酸（ALA）介导的声动力疗法（ALA-SDT）对血管平滑肌细胞（VSMC）的影响，VSMC是再狭窄的一个成因，重点关注SDT诱导的表型转换。用ALA（1 mM，24小时）培养血清诱导的去分化VSMC，并暴露于超声（0.8 W/cm²）5分钟。结果表明，ALA-SDT抑制了VSMC的迁移和增殖，并增强了VSMC中分化表型标志物的表达。此外，ALA-SDT增加了VSMC内活性氧的积累以及磷酸化的p38丝裂原活化蛋白激酶。抑制活性氧升高或p38丝裂原活化蛋白激酶活性可消除ALA-SDT诱导的VSMC中平滑肌22α（SM22α）的表达。综上所述，这些结果表明，ALA-SDT通过活性氧和激活的p38丝裂原活化蛋白激酶促进VSMC表型从去分化状态向分化状态的转变。
