SFRP4 Reduces Atherosclerosis Plaque Formation in ApoE Deficient Mice

Area of Science:

• Cardiovascular Research
• Metabolic Disease Research
• Atherosclerosis Studies

Background:

• Secreted frizzled related protein 4 (SFRP4) is implicated in metabolic and cardiovascular diseases.
• Evidence for SFRP4's anti-atherosclerosis effects, particularly in ApoE knockout (KO) mouse models, is limited.

Purpose of the Study:

• To investigate the anti-atherosclerosis effect of SFRP4 in apolipoprotein E knockout (ApoE KO) mice.
• To explore the molecular mechanisms underlying SFRP4's potential role in mitigating atherosclerosis.

Main Methods:

• ApoE KO mice were fed a high-fat (western) diet for 12 weeks.
• Adenovirus-mediated overexpression of SFRP4 (Ad-SFRP4) was administered via tail vein injection.
• Aortic atherosclerotic plaque area, plasma lipid profiles, and gene expression (RNA sequencing) were analyzed.

Main Results:

• Overexpression of SFRP4 significantly reduced the area of atherosclerotic plaques in the aorta of ApoE KO mice.
• Ad-SFRP4 administration led to elevated levels of high-density lipoprotein cholesterol (HDL-C).
• RNA sequencing identified 96 differentially expressed genes in aortic lesions, enriched in 10 signaling pathways related to metabolism and disease.

Conclusions:

• SFRP4 demonstrates a significant protective effect against the development of atherosclerotic plaque in the aorta.
• SFRP4 may exert its anti-atherosclerosis effects by modulating specific gene expression pathways involved in metabolism and disease.
• SFRP4 represents a potential therapeutic target for managing atherosclerosis.