Accumulating evidence suggests that atherosclerosis (AS) is the underlying cause of vascular diseases, including heart disease and stroke. Ultrasound-targeted microbubble destruction (UTMD) technology provides a tolerable, efficient and effective system for drug delivery and gene transfection, which has broad application prospects in the treatment of AS. In addition, glycogen synthase kinase (GSK)-3β has been implicated as a potentially valuable therapeutic agent for AS treatment; however, the specific molecular mechanisms remain unknown. Therefore, this study was conducted to explore the effect of downregulation of GSK-3β expression via UTMD on atherosclerotic plaque stability. We established a THP-1 macrophage-derived foam cell model in vitro and an atherosclerotic plaque model in the right common carotid artery of New Zealand rabbits. We determined levels of the relevant vulnerable plaque stability elements. The results indicate that GSK-3β was upregulated in the foam cells and in atherosclerotic rabbits. Downregulation of GSK-3β expression by UTMD suppressed vulnerable plaque factors and inflammation in vitro and in vivo, changed the cytoskeleton of the foam cells in vitro, increased Young's modulus and decreased the peak intensity of atherosclerotic plaque in vivo. Moreover, GSK-3β inhibition by UTMD did not influence the viability of the foam cells. Collectively, our results indicate that GSK-3β could be a potential target for anti-atherogenic interventions and, in particular, can improve the stability of AS plaques in combination with UTMD.

越来越多的证据表明，动脉粥样硬化 (AS) 是血管疾病的根本原因，包括心脏病和中风。超声靶向微泡破坏（UTMD）技术为药物递送和基因转染提供了可耐受、高效和有效的系统，在AS的治疗中具有广阔的应用前景。此外，糖原合酶激酶 (GSK)-3β 已被认为是治疗 AS 的潜在有价值的治疗剂。然而，具体的分子机制仍然未知。因此，本研究旨在探讨通过UTMD下调 GSK-3β 表达对动脉粥样硬化斑块稳定性的影响。我们在体外建立了THP-1巨噬细胞来源的泡沫细胞模型新西兰兔右颈总动脉的动脉粥样硬化斑块模型。我们确定了相关易损斑块稳定性元素的水平。结果表明 GSK-3β 在泡沫细胞和动脉粥样硬化兔中上调。UTMD下调GSK-3β表达在体外和体内抑制易损斑块因子和炎症，改变体外泡沫细胞的细胞骨架，增加杨氏模量并降低体内动脉粥样硬化斑块的峰值强度。. 此外，UTMD 对 GSK-3β 的抑制不影响泡沫细胞的活力。总的来说，我们的结果表明 GSK-3β 可能是抗动脉粥样硬化干预的潜在目标，特别是可以与 UTMD 结合提高 AS 斑块的稳定性。