Comparative Study on Metabolic Regulation of SAP Deletion in Normal Mice and Atherosclerotic Mice

Yifan Zhu; Shuhan Xie; Hailong Shu; Yiqing Lu; Jiawei Guo; Qian Li; Yongli Zhang; Yongxia Yang

doi:10.53941/hm.2025.100020

Abstract

SAP is a serum protein associated with an increased risk of cardiovascular events, and studies have uncovered a significant positive correlation between SAP and the pathogenesis of atherosclerosis. Our previous research found that SAP deficiency in ApoE^−/− mice significantly reduced the formation of foam cells and the expression of pro-inflammatory factors, and caused significant metabolic changes. However, it is still unclear whether SAP deficiency has the same function and metabolic regulation effect on normal background mice. In this study, C57 and SAP^−/− mice were used as models. Histopathological examinations were performed to evaluate the histomorphological changes of heart, liver, spleen, lung and kidney tissues in SAP^−/− mice. The results showed that there were no significant histopathology changes in the main organs of SAP^−/− mice, but there were significant differences in the serum metabolic profiles between C57 and SAP^−/− mice. It was found that the deficiency of SAP in both C57 and ApoE^−/− mice upregulated choline, but the regulatory trends on LDL/VLDL were different. Acetate and pyruvate were regulated by SAP deficiency in ApoE^−/− mice, but not in C57 mice. In addition, the deletion of SAP also caused significant changes in formate, tyrosine, glycine, glucose, TMAO, taurine, citrate, succinate, and histidine in C57 context, which were not detected in the context of atherosclerosis. In summary, this study indicates that the metabolic regulation of the SAP gene is not only related to the gene itself but also related to the physiological or pathological state of the organism.

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