Mechanism of lactoferrin in alleviating atherosclerosis by inhibiting senescence-associated secretory phenotype of macrophages
LIANG Jingwei
CHEN Jiajia
JIANG Xuefang
PENG Sujuan
LU Yanlin
LIU Dinglang
DING Jiuyang
XIA Bing
Abstract：Objective Our investigate the correlation between lactoferrin(LTF)expression and severity of coronary stenosis,and the potential mechanism of LTF in regulating macrophage senescence-associated secretory phenotype(SASP).Methods The arterial samples from the left anterior descending coronary artery were collected from the corpses in Forensic Identification Center of Guizhou Medical University from January 2020 to December 2023,and divided into a control group(n=20),a mild coronary artery disease(CAD)group(n=20,stenosis＜50％),and a severe CAD group(n=20,stenosis ≥50％).Western blotting and immunohistochemical staining were used to detect the protein expression of LTF and SASP markers,such as IL-1β,IL-6,matrix metalloproteinase 9(MMP-9),and cyclin-dependent kinase inhibitor 2A(CDKN2A or P16).Pearson correlation analysis was employed to study the relationship between LTF and IL-1β,IL-6,MMP-9,and P16.In vitro,there were four groups of cells,that is,PMA group(macrophages differentiated from THP-1 monocytes by phorbol ester),ox-LDL group[foam cells induced by oxidized low-density lipoprotein(ox-LDL)],siRNA-NC group(foam cells transfected with non-targeting siRNA,siRNA-negative control),and siRNA-LTF group(foam cells transfected with LTF-targeting siRNA).Intracellular lipid levels were observed by Oil Red O staining.Cell senescence was detected by senescence-associated β-galactosidase staining.The protein expression levels of IL-1β,IL-6,MMP-9 and P16 were measured by Western blotting.The expression and localization of LTF and P16 were observed with immunofluorescence assay.Results The degree of stenosis and the protein levels of LTF,IL-1β,IL-6,MMP-9,and P16 in coronary artery tissues were significantly higher in the mild CAD group than the control group(P＜0.05,P＜0.01),and further elevated in the severe CAD group than the mild CAD group(P＜0.05,P＜0.01).Correlation analysis showed LTF was positively correlated with the expression levels of IL-1β,IL-6,MMP-9 and P16(r=0.895,r=0.912,r=0.917,r=0.855,P＜0.01).In in vitro experiments,the ox-LDL group exhibited significantly more lipid deposition,higher rate of senescent cell,and increased protein levels of IL-1β,IL-6,MMP-9,P16,and LTF when compared with the PMA group(P＜0.05,P＜0.01);The siRNA-LTF group showed significantly increased levels of the aforementioned indicators compared to the ox-LDL group,while LTF expression was obviously reduced(P＜0.05,P＜0.01).Conclusion LTF expression is upregulated in coronary atherosclerotic plaques and positively correlated with coronary stenosis severity.LTF can alleviate atherosclerosis progression by inhibiting macrophage senescence.
Keywords：lactoferrincoronary artery diseasemacrophagescellular senescence
Publication Date：2026-03-15
Online Publishing Date：2026-03-31(First online date of this platform, not the publication date of the document)
Pages：5( 289-293 )