Furthermore, CD68+ VSMCs’ proliferation caused by TLR4 activation42 could be observed in our scRNA-seq results and IF staining in plaque, indicating that the PAD4 (hi) CD68+ SMC had the potential to maintain its population and mediate positive feedback of pro-inflammation, thereby promoting atherosclerosis plaque burden (Shown in Fig. 6). This evidence concerns the gene TLR4 and atherosclerosis.