The effects of ultrasound-targeted microbubble destruction (UTMD) carrying IL-8 monoclonal antibody on the inflammatory responses and stability of atherosclerotic plaques

• Main Authors: Hanning Yang, Yue Sun, Jia Wei, Lirong Xu, Yueyue Tang, Lihong Yang, Xiaoqi Zhang, Yongping Lu
• Format: Article
• Language: English
• Published: Elsevier 2019-10-01
• Series: Biomedicine & Pharmacotherapy
• Subjects: Atherosclerosis; Contrast-enhanced ultrasonography; Ultrasound-targeted microbubble destruction; Inflammatory response
• Online Access: http://www.sciencedirect.com/science/article/pii/S075333221930811X

This study investigated the value of using ultrasound-targeted microbubble destruction (UTMD) to deliver an IL-8 monoclonal antibody to inhibit the inflammatory response and increase plaque stability in a rabbit model of atherosclerosis (AS). An abdominal aortic atherosclerotic plaque model was established in sixty 4-week-old male New Zealand rabbits. The rabbits were fed a high-fat diet for 12 weeks. On the 12th week, the abdominal aorta was subjected to both balloon-induced mechanical injury and bovine serum albumin-induced immunological injury. After these injuries were established, the rabbits were fed a high-fat diet for 8 additional weeks. On the 20th week, the rabbits were divided into three groups: the pretreatment (PT) group, the control group, and the IL-8 group. The ultrasonic parameters and histological data associated with the plaques from the PT group were acquired on the 20th week after targeted contrast-enhanced ultrasonography (CEUS) was performed. The rabbits in the IL-8 and control groups received targeted CEUS and UTMD every 2 weeks. A targeted contrast agent carrying IL-8 monoclonal antibody was used for the IL-8 group, whereas normal saline was used for the control group. The rabbits in these two groups underwent the same procedure four times beginning during the 20th week. On the 26th week after UTMD, ultrasonic parameters and histological data were collected. The peak intensity (PI), microvessel density (MVD), and macrophage count of the PT group were significantly higher than those of both the control and IL-8 groups (P < 0.05). Additionally, these three parameters were higher in the control group than in the IL-8 group (P < 0.05). The two-dimensional (2D) ultrasonic parameters, including the maximum thickness of the plaque and the intima-media thickness (IMT), did not differ significantly among the three groups (P > 0.05). PI, MVD, and macrophage count were positively correlated with each other (r=0.564, r=0.6034, and r=0.536, respectively; P<0.05). UTMD-delivered IL-8 monoclonal antibodies alleviate inflammation within atherosclerotic plaques. UTMD is a novel and effective method for plaque stabilization.