The excessive proliferation, endothelial migration, and phenotype transformation of vascular smooth muscle cells (VSMC) lead to increased extracellular matrix secretion, which induces vascular intimal hyperplasia, which is an important restenosis mechanism after vascular injury. In our study, we verified the cytotoxicity of SiO₂ nanoparticles to VSMC. To explore the role of endothelial repairs and molecular mechanisms after vascular injuries, we sequenced the transcriptome of injured vessels in the carotid artery of mice. The results showed the differentially expressed genes in normal vascular tissues, and that vascular tissues were mainly enriched with NF-κB signaling pathways, chemokine signaling pathways and other biological functions, by the leukocyte activation and adhesion of the KEGG pathway in the immune response, and by DNA binding, DNA transcription regulatory region binding, and other molecular functions. Core proteins included PRKCB, STAT4, CCL5, and BCL-2. To verify the roles of these core proteins, RT-qPCR andWestern blot techniques were used to detect their transcription and translation levels, and HE staining was used to detect morphological changes in blood vessels. To further clarify the role of core proteins in VSMC, PRKCB over expression plasmids were constructed, and the RT-qPCR and Western blot techniques were again used to detect the expression of core proteins. The results showed that the levels of transcription and translation, and of PRKCB and STAT4 phosphorylation, increased significantly after vascular injury, and then noticeably decreased three days later- and that CCL5 and Bcl-2 expression trends were consistent with this. HE staining showed that when the vascular endothelium was damaged, smooth muscle cells proliferated significantly, and that the intima thickened three days after vascular injury. After over expression of PRKCB, the expression and activation of STAT4, CCL5, and Bcl-2 significantly increased, α-SMA and Vimentin were down-regulated, OPN was up-regulated, and VSMC activity was enhanced. From these results, it could be concluded that PRKCB is activated by vascular injury, and that over-activation of PRKCB promotes activation of STAT4 and the expression of CCL5 and BCL-2-which in turn leads to enhanced VSMC activity and transformation of its contraction phenotype to the secretion phenotype. We were also able to establish that the cytotoxicity of SiO₂ nanoparticles to VSMC was positively correlated with dose and time.