Extracellular DNA traps (ETs) represent an immune response by which cells release essential materials like chromatin and granular proteins. Previous studies have demonstrated that the transdifferentiation of vascular smooth muscle cells (VSMCs) plays a crucial role in atherosclerosis. This study seeks to investigate the interaction between CD68+ VSMCs and the formation of ETs and highlight its function in atherosclerosis. Here we show that ETs are inhibited, and atherosclerotic plaque formation is alleviated in male Myh11CrePad4flox/flox mice undergoing an adeno-associated-virus-8 (AAV8) mediating overexpression of proprotein convertase subtilisin/kexin type 9 mutation (PCSK9) injection and being challenged with a high-fat diet. Obvious ETs generated from CD68+ VSMCs are inhibited by Cl-amidine and DNase I in vitro. By utilizing VSMCs-lineage tracing technology and single-cell RNA sequencing (scRNA-seq), we demonstrate that the ETs from CD68+ VSMCs influence the progress of atherosclerosis by regulating the direction of VSMCs’ transdifferentiation through STING-SOCS1 or TLR4 signaling pathway.

Atherosclerosis (AS) is a chronic inflammatory disease, which may lead to high morbidity and mortality. Currently, the clinical treatment strategy for AS is administering drugs and performing surgery. However, advanced therapy strategies are urgently required because of the deficient therapeutic effects of current managements. Increased number of energy conversion-based organic or inorganic materials has been used in cancer and other major disease treatments, bringing hope to patients with the development of nanomedicine and materials. These treatment strategies employ specific nanomaterials with specific own physiochemical properties (external stimuli: light or ultrasound) to promote foam cell apoptosis and cholesterol efflux. Based on the pathological characteristics of vulnerable plaques, energy conversion-based nano-therapy has attracted increasing attention in the field of anti-atherosclerosis. Therefore, this review focuses on recent advances in energy conversion-based treatments. In addition to summarizing the therapeutic effects of various techniques, the regulated pathological processes are highlighted. Finally, the challenges and prospects for further development of dynamic treatment for AS are discussed.