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Updated: Jan 16, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Factor XI Deficiency in apoE/FXI Double-Knockout Mice Decreases Atherosclerosis by Lowering MSR1 mRNA Expression
Reut Shnerb Ganor1,2, Elvezia M Paraboschi3,4, Duga Stefano3,4
1The Bert W. Strassburger Metabolic Center, Sheba Medical Center, Tel-Hashomer, Israel.
Objective:
Atherosclerosis remains a leading cause of global morbidity and mortality despite cholesterol-lowering drugs and risk factor management. In mice, the absence of coagulation factor XI (FXI) on an apolipoprotein E (apoE)-/- genetic background has been shown to reduce atherosclerosis. This study examined the molecular pathways through which FXI influences the development of atherosclerosis.
Methods:
Laser capture microdissection of plaques from the aortic sinus of apoE/factor XI double knockout (DKO) and apoE knockout (KO) mice was performed at 24 weeks. RNA-seq and the NanoString technique were used to analyze the extracted plaques. Immunohistochemical analysis of the atherosclerotic layers was also conducted.
Results:
Among 15,353 expressed genes, 64 showed significant differences between the 2 groups. Gene set enrichment analysis, specifically targeting metabolic pathways, identified upregulation of 8 pathways in atherosclerotic plaques of apoE KO mice; seven of these pathways were classified as related to inflammatory processes. Using an immunological panel containing 547 genes linked to inflammatory and immunological processes, a statistically significant difference was observed in the expression of macrophage scavenger receptor 1 (MSR1) between DKO mice and apoE KO mice (adjusted p-value=0.0015).
Conclusion:
Downregulated expression of MSR1 within the atherosclerotic plaques of apoE/FXI DKO mice compared to apoE KO mice was associated with significantly reduced atherosclerosis. Targeting FXI may therefore represent a promising anti-atherogenic therapeutic strategy in addition to its known antithrombotic effects.
Insights
Targeting coagulation factor XI (FXI) reduced atherosclerosis in mice by downregulating macrophage scavenger receptor 1 (MSR1). This suggests FXI is a potential therapeutic target for atherosclerosis beyond its antithrombotic effects.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Immunology
Background:
- Atherosclerosis is a major cause of death globally, inadequately managed by current therapies.
- Absence of coagulation factor XI (FXI) in mice with apolipoprotein E knockout (apoE-/-) reduces atherosclerosis.
- The molecular mechanisms by which FXI influences atherosclerosis are not fully understood.
Purpose of the Study:
- To investigate the molecular pathways involved in FXI-mediated atherosclerosis.
- To identify specific genes and pathways affected by the absence of FXI in atherosclerosis.
Main Methods:
- Laser capture microdissection of aortic sinus plaques from apoE/FXI double knockout (DKO) and apoE knockout (KO) mice.
- RNA sequencing and NanoString analysis of plaque RNA.
- Immunohistochemical analysis of atherosclerotic lesions.
Main Results:
- 64 out of 15,353 genes showed significant differential expression between DKO and KO mice.
- Gene set enrichment analysis revealed 8 upregulated metabolic pathways in apoE KO mice, 7 linked to inflammation.
- Significantly lower expression of macrophage scavenger receptor 1 (MSR1) was observed in DKO mice compared to apoE KO mice.
Conclusions:
- Downregulated MSR1 in apoE/FXI DKO mice correlated with reduced atherosclerosis.
- Targeting FXI presents a potential anti-atherogenic therapeutic strategy.
- FXI inhibition may offer dual benefits: antithrombotic and anti-atherogenic effects.
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