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

Juhua Dan; Xin Sun; Wanlu Li; Yun Zhang; Xuesong Li; Haobo Xu; Zhitao Li; Zhen Tian; Shuyuan Guo; Jianting Yao; Weidong Gao; Ye Tian

doi:10.1016/j.ultrasmedbio.2014.12.664

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

Ultrasound Med Biol. 2015 Jun;41(6):1681-9. doi: 10.1016/j.ultrasmedbio.2014.12.664. Epub 2015 Mar 18.

Authors

Juhua Dan¹, Xin Sun², Wanlu Li¹, Yun Zhang², Xuesong Li¹, Haobo Xu², Zhitao Li¹, Zhen Tian¹, Shuyuan Guo², Jianting Yao², Weidong Gao³, Ye Tian⁴

Affiliations

¹ 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.
² Division of Cardiology, First Affiliated Hospital, Harbin Medical University, Harbin, China.
³ 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.
⁴ 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: [email protected].

PMID: 25796412
DOI: 10.1016/j.ultrasmedbio.2014.12.664

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.

Keywords: 5-Aminolevulinic acid; Reactive oxygen species; Sonodynamic therapy; Vascular smooth muscle cell; p38 mitogen-activated protein kinase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aminolevulinic Acid / pharmacology*
Animals
Blotting, Western
Cell Differentiation / drug effects
Cell Proliferation / drug effects
Cells, Cultured
Flow Cytometry
High-Energy Shock Waves*
Mice
Muscle, Smooth, Vascular / drug effects
Muscle, Smooth, Vascular / metabolism*
Phenotype*
Photosensitizing Agents / pharmacology
Reactive Oxygen Species / metabolism*
Signal Transduction / drug effects
p38 Mitogen-Activated Protein Kinases / drug effects
p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

Photosensitizing Agents
Reactive Oxygen Species
Aminolevulinic Acid
p38 Mitogen-Activated Protein Kinases