title: 5-Aminolevulinic Acid-Mediated Sonodynamic Therapy Promotes Phenotypic Switching from Dedifferentiated to Differentiated Phenotype via Reactive Oxygen Species and p38 Mitogen-Activated Protein Kinase in Vascular Smooth Muscle Cells.
abstract: 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.
authors: 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.
authors: Juhua
authors: J
authors: Dan
authors: Division of Cardiology, First Affiliated Hospital, Harbin Medical University, Harbin, China.
authors: Xin
authors: X
authors: Sun
authors: 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.
authors: Wanlu
authors: W
authors: Li
authors: Division of Cardiology, First Affiliated Hospital, Harbin Medical University, Harbin, China.
authors: Yun
authors: Y
authors: Zhang
authors: 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.
authors: Xuesong
authors: X
authors: Li
authors: Division of Cardiology, First Affiliated Hospital, Harbin Medical University, Harbin, China.
authors: Haobo
authors: H
authors: Xu
authors: 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.
authors: Zhitao
authors: Z
authors: Li
authors: 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.
authors: Zhen
authors: Z
authors: Tian
authors: Division of Cardiology, First Affiliated Hospital, Harbin Medical University, Harbin, China.
authors: Shuyuan
authors: S
authors: Guo
authors: Division of Cardiology, First Affiliated Hospital, Harbin Medical University, Harbin, China.
authors: Jianting
authors: J
authors: Yao
authors: 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; Department of Anesthesiology, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Weidong
authors: W
authors: Gao
authors: 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. Electronic address: Yetian@ems.hrbmu.edu.cn.
authors: Ye
authors: Y
authors: Tian
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D019220:High-Energy Shock Waves; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D017319:Photosensitizing Agents / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*
chemical_list: D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D000622:Aminolevulinic Acid; D048051:p38 Mitogen-Activated Protein Kinases
keywords: 5-Aminolevulinic acid; Reactive oxygen species; Sonodynamic therapy; Vascular smooth muscle cell; p38 mitogen-activated protein kinase