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

Zhitao Li; Xin Sun; Shuyuan Guo; Liping Wang; Tengyu Wang; Chenghai Peng; Wei Wang; Zhen Tian; Ruibo Zhao; Wenwu Cao; Ye Tian

doi:10.1160/TH14-12-1030

Thrombosis and Haemostasis, Inhaltsverzeichnis

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^*

¹Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, China

²Division of Pathophysiology, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin, China

,

Xin Sun^*

¹Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, China

²Division of Pathophysiology, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin, China

³Laboratory of Photo- and Sono-THeranostic Technologies and Condensed Matter Science and Technology Institute, Harbin Institute of Technology, Harbin, China

,

Shuyuan Guo^*

¹Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, China

,

Liping Wang

¹Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, China

⁴Division of Geratology, the Second Affiliated Hospital, Harbin Medical University, Harbin, China

,

Tengyu Wang

¹Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, China

,

Chenghai Peng

⁵Emergency Department, the Fourth Affiliated Hospital, Harbin Medical University, Harbin, China

,

Wei Wang

¹Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, China

,

Zhen Tian

²Division of Pathophysiology, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin, China

,

Ruibo Zhao

⁶Division of Pathology, Harbin Medical University, Harbin, China

,

Wenwu Cao

³Laboratory of Photo- and Sono-THeranostic Technologies and Condensed Matter Science and Technology Institute, Harbin Institute of Technology, Harbin, China

⁷Materials Research Institute, The Pennsylvania State University, University Park, Pennsylvania, USA

,

Ye Tian^*

¹Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, China

²Division of Pathophysiology, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin, China

› Institutsangaben

Abstract

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

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Referenzen

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