Author + information
- Received July 29, 2019
- Revision received October 7, 2019
- Accepted October 7, 2019
- Published online January 27, 2020.
- Jianting Yao, MD, PhDa,∗,
- Weiwei Gao, MDa,∗,
- Yu Wang, MD, PhDa,
- Lu Wang, PhDa,
- Kamal Diabakte, MDa,
- Jinyang Li, MDb,c,
- Jiemei Yang, MDa,
- Yongxing Jiang, MDa,
- Yuerong Liu, MDa,
- Shuyuan Guo, MDa,
- Xuezhu Zhao, MDa,
- Zhengyu Cao, MDa,
- Xi Chen, MD, PhDa,
- Qiannan Li, MDa,
- Haiyu Zhang, PhDa,
- Wei Wang, MDa,
- Zhen Tian, PhDb,c,
- Bicheng Li, MD, PhDa,
- Fang Tian, MD, PhDa,
- Guodong Wu, MDa,
- Shirin Pourteymour, PhDd,
- Xi Huang, MDa,
- Fancheng Tan, MDb,c,
- Xiaoru Cao, MDb,c,
- Zhuowen Yang, MDa,
- Kang Li, PhDe,
- Yan Zhang, PhDf,
- Yong Li, MD, PhDg,
- Zhiguo Zhang, PhDh,
- Hong Jin, MD, PhDd,∗∗ ( and )
- Ye Tian, MD, PhDa,b,c,∗ ()
- aDepartment of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, People’s Republic of China
- bDepartment of Pathophysiology and Key Laboratory of Cardiovascular Pathophysiology, Harbin Medical University, Harbin, People’s Republic of China
- cKey Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, People’s Republic of China
- dDepartment of Medicine, Karolinska Institute, Stockholm, Sweden
- eDepartment of Epidemiology and Biostatistics, Harbin Medical University, Harbin, People’s Republic of China
- fSchool of Life Science and Technology, Research Center for Computational Biology, Harbin Institute of Technology, Harbin, People’s Republic of China
- gDepartment of Positron Emission Tomography–Computed Tomography, the First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China
- hLaboratory of Photo- and Sono-theranostic Technologies and Condensed Matter Science and Technology Institute, Harbin Institute of Technology, Harbin, People’s Republic of China
- ↵∗Address for correspondence:
Dr. Ye Tian, Department of Cardiology, The First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, 23 Youzheng Street, Harbin 150001, China.
- ↵∗∗Dr. Hong Jin, Molecular Vascular Medicine, Medicine Department, Bioclinicum, Akademiska Stråket 1, J8:20, Karolinska University Hospital, 17164 Solna, Sweden.
• DVDMS-SDT reduces neovascularization in late-stage atherosclerotic lesions in both rabbit and mouse models.
• DVDMS-SDT enhances macrophage foam cell apoptosis, which in turn induces neovessel endothelial cell apoptosis and inhibits its proliferation, migration, and tubulogenesis, termed apoptosis-induced apoptosis.
• Mechanistically, DVDMS-SDT induces macrophage foam cell apoptosis via mitochondrial-caspase pathway, which activates caspase 3 to cleave SP-1, leading to the reduction of HIF-1α and VEGF-A.
• In the pilot translational study, DVDMS-SDT reduces plaque angiogenesis and inhibits vessel inflammation.
During atherosclerosis plaque progression, pathological intraplaque angiogenesis leads to plaque rupture accompanied by thrombosis, which is probably the most important cause of arteries complications such as cerebral and myocardial infarction. Even though few treatments are available to mitigate plaque rupture, further investigation is required to develop a robust optimized therapeutic method. In this study using rabbit and mouse atherosclerotic models, sinoporphyrin sodium (DVDMS)-mediated sonodynamic therapy reduced abnormal angiogenesis and plaque rupture. Briefly, DVDMS is injected to animals, and then the plaque was locally exposed to pulse ultrasound for a few minutes. Furthermore, a small size clinical trial was conducted on patients with atherosclerosis. Notably, a significant reduction of arterial inflammation and angiogenesis was recorded following a short period of DVDMS-mediated sonodynamic therapy treatment. This beneficial outcome was almost equivalent to the therapeutic outcome after 3-month intensive statin treatment.
- apoptosis-induced apoptosis
- atherosclerotic plaque
- endothelial cell
- sonodynamic therapy
↵∗ Drs. Yao and Gao contributed equally to this work and are joint first authors.
This work was funded by the State Key Program of the Natural Science Foundation of China (81530052 to Dr. Tian), the major scientific instrument equipment development project of China (81727809 to Dr. Y. Tian), and the Magnus Bergvalls Stiftelse Foundation of Sweden (2018-02582 to Dr. Jin). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received July 29, 2019.
- Revision received October 7, 2019.
- Accepted October 7, 2019.
- 2020 The Authors