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Thromb Haemost 2015; 114(04): 793-803
DOI: 10.1160/TH14-12-1030
New Technologies, Diagnostic Tools and Drugs
Schattauer GmbH

Rapid stabilisation of atherosclerotic plaque with 5-aminolevulinic acid-mediated sonodynamic therapy

Zhitao Li   *
1   Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, China
2   Division of Pathophysiology, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin, China
,
Xin Sun   *
1   Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, China
2   Division of Pathophysiology, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin, China
3   Laboratory of Photo- and Sono-THeranostic Technologies and Condensed Matter Science and Technology Institute, Harbin Institute of Technology, Harbin, China
,
Shuyuan Guo   *
1   Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, China
,
Liping Wang
1   Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, China
4   Division of Geratology, the Second Affiliated Hospital, Harbin Medical University, Harbin, China
,
Tengyu Wang
1   Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, China
,
Chenghai Peng
5   Emergency Department, the Fourth Affiliated Hospital, Harbin Medical University, Harbin, China
,
Wei Wang
1   Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, China
,
Zhen Tian
2   Division of Pathophysiology, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin, China
,
Ruibo Zhao
6   Division of Pathology, Harbin Medical University, Harbin, China
,
Wenwu Cao
3   Laboratory of Photo- and Sono-THeranostic Technologies and Condensed Matter Science and Technology Institute, Harbin Institute of Technology, Harbin, China
7   Materials Research Institute, The Pennsylvania State University, University Park, Pennsylvania, USA
,
Ye Tian   *
1   Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, China
2   Division of Pathophysiology, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin, China
› Author Affiliations
Further Information

Publication History

Received: 11 December 2014

Accepted after major revision: 07 May 2015

Publication Date:
29 November 2017 (online)

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Summary

5-Aminolevulinic acid-mediated sonodynamic therapy (ALA-SDT) effectively induces the apoptosis of atherogenic macrophages, but whether it can stabilise atherosclerotic plaque in vivo is unclear. Here, we used an animal model to evaluate the effects of ALA-SDT on plaque stabilisation. Sixty rabbits were induced atherosclerotic plaques in the femoral artery with a combination of silastic tube placement with atherogenic diet, and randomly assigned into control (n = 12) and SDT (n = 48) groups. In the SDT group, after intravenous injected with ALA (60 mg/kg) animals underwent the treatment of ultrasound with intensities of 0.75, 1.00, 1.50 and 2.00 W/cm2 (n = 12 for each intensity). Seven days after the treatment, the plaque disruption assay was performed to test plaque stability. We found that ALA-SDT with ultrasound intensity of 1.5 W/cm2 showed the strongest efficacy to stabilise plaques. Under this condition, the frequency of plaque disruption decreased by 88 % (p < 0.01), positive area of macrophages reduced by 94 % (p < 0.001) and percentage content of lipids dropped by 60 % (p < 0.001), while percentage content of collagens increased by 127 % (p < 0.001). We also found that the plaque stabilisation by ALA-SDT was associated with increased macrophage apoptosis and apoptotic cell clearance. Moreover, ALA-SDT decreased the contents and activities of matrix metalloproteinase-2,9 and increased the levels of tissue inhibitors of matrix metalloproteinase-1,2 in plaques. Our studies demonstrate that ALA-SDT promotes plaque stabilisation by inducing macrophage elimination and inhibiting matrix degradation. This method might be a promising regimen for atherosclerosis therapy.

Keywords

Sonodynamic therapy - atherosclerosis - plaque disruption - macrophage - matrix metalloproteinase

* Zhitao Li, Xin Sun and Shuyuan Guo contributed equally to this study.


 

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