Sonodynamic Therapy Suppresses Neovascularization in Atherosclerotic Plaques via Macrophage Apoptosis-Induced Endothelial Cell Apoptosis

JACC Basic Transl Sci. 2019 Dec 26;5(1):53-65. doi: 10.1016/j.jacbts.2019.10.007. eCollection 2020 Jan.

Abstract

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.

Keywords: ALA, 5-aminolevulinic acid; ApoE, apolipoprotein E; ChIP, chromatin immunoprecipitation; DVDMS, sinoporphyrin sodium; DVDMS-SDT, sinoporphyrin sodium-mediated sonodynamic therapy; HIF, hypoxia inducible factor; HUVEC, human umbilical vein endothelial cells; MVE, normalized maximal video-intensity enhancement; SDT, sonodynamic therapy; SP, specificity protein; TBR, target-to-background ratio; VEGF-A, vascular endothelial growth factor A; apoptosis-induced apoptosis; atherosclerotic plaque; endothelial cell; macrophage; neovascularization; sonodynamic therapy.