To systematically elucidate the molecular mechanism by which Porphyromonas gingivalis lipopolysaccharide (P. gingivalis-LPS) modulates carnitine palmitoyltransferase 1A (CPT1A) to influence metabolic reprogramming and apoptosis in foam cells, and to explore the potential link between periodontal pathogen infection and the progression of atherosclerosis.

Transcriptome sequencing was employed to analyze the whole-genome expression profiles of foam cells stimulated by P. gingivalis-LPS. Differentially expressed genes (DEGs) were screened, and functional enrichment analysis was conducted using bioinformatics methods. Further validation of the core regulatory role of CPT1A in lipid metabolism and apoptosis was performed through gene overexpression and apoptosis assays.

Transcriptomic analysis identified 427 DEGs (318 upregulated and 109 downregulated) under the thresholds of |log₂FC|>1 and FDR<0.05. GO and KEGG enrichment analyses based on these DEGs indicated significant enrichment in lipid- and sterol-related biological processes, as well as the PPAR signaling pathway, fatty acid metabolism, and steroid biosynthesis. GSEA results showed that cholesterol/sterol biosynthesis-related pathways were negatively enriched, whereas fatty acid transport and adaptive lipid metabolic processes were positively enriched. In addition, apoptosis-related pathways, including the p53 pathway, were also positively enriched. Among these, CPT1A expression was markedly elevated and confirmed as a key regulator. Functional studies demonstrated that CPT1A overexpression enhanced cell viability and suppressed apoptosis (P<0.05) .

CPT1A may mediate the promotion of atherosclerotic foam cell pathogenesis by periodontal pathogen infection via coordinating lipid metabolic reprogramming and apoptosis resistance.