Abstract: Specific proteins (Sp) are a well-known family of transcription factors. Sp1 as a key transcription factor, specific protein 1 (Sp1) regulates the pathological process of atherosclerosis (AS) through post-translational modification (PTMs). Phosphorylation and acetylating affect lipid metabolism, plaque stability, proliferation of vascular smooth muscle cells (VSMCs) and endothelial dysfunction by regulating DNA binding capacity and transcriptional activity. Phosphorylated Sp1 enhances the binding of ABCA1 and LDLR promoters to promote cholesterol efflux. Acetylated Sp1 up-regulates SR-BI expression and inhibits lipid accumulation by recruiting p300. Melatonin promotes collagen deposition through Akt/Sp1 pathway, and atorvastatin inhibits the binding of Sp1 and TLR2 to reduce the release of inflammatory factors. AngⅡ/PKC-ζ pathway drives PDGF-D expression to promote intimal thickening, while FGF-2/ERK pathway inhibits PDGFR-α transcription through Sp1 phosphorylation and delays plaque progression. S-sulfhydrylation and ubiquitination modifications improve vasodilatation and oxidative stress by stabilizing Sp1 and enhancing its binding to VEGFR-2. In this paper, the regulatory network of Sp1 PTMs in AS is analyzed, and potential therapeutic strategies targeting modification sites (such as Thr453/Ser702) and natural compounds (such as Cy3G and kaempferol) are proposed to provide theoretical basis for precise intervention of AS.

Key words: atherosclerosis, specific protein 1(Sp1), post-translational modification, cell signaling transduction, mechanism of action