A human apolipoprotein E mimetic peptide reduces atherosclerosis in aged apolipoprotein E null mice

Area of Science:

• Cardiovascular Research
• Molecular Biology
• Pharmacology

Background:

• Apolipoprotein E (apoE) is crucial for lipid metabolism and possesses anti-atherogenic properties.
• Previous studies showed apoE mimetic peptides can reduce inflammation and atherosclerosis.
• Aged female apoE null mice with existing lesions provide a model for advanced atherosclerosis.

Purpose of the Study:

• To investigate the therapeutic potential of a new human apoE mimetic peptide, hEp, in reducing atherosclerotic lesion development.
• To evaluate hEp's effects on lipid levels, inflammation, and oxidative stress in vivo.
• To assess hEp's efficacy in aged female apoE null mice with pre-existing atherosclerotic lesions.

Main Methods:

• In vitro studies assessed hEp's effect on cholesterol accumulation and inflammatory cytokine expression in macrophages.
• In vivo studies involved intravenous injection of Lv-hEp-GFP lentivirus into 9-month-old apoE(-/-) mice.
• Mice were fed a chow diet for 18 weeks, with subsequent analysis of plasma lipids, aortic lesions, hepatic gene expression, and plasma enzyme activities.

Main Results:

• hEp significantly reduced cholesterol and inflammatory cytokines (TNFα, IL-6) in macrophages.
• Hepatic hEp expression in mice led to reduced plasma VLDL and LDL cholesterol levels.
• Aortic atherosclerotic lesions were significantly decreased in hEp-treated mice, accompanied by increased LDL receptor expression and reduced liver inflammation.
• hEp treatment also improved antioxidant markers (increased paraoxonase-1 activity) and reduced inflammatory markers (decreased myeloperoxidase and serum amyloid A).

Conclusions:

• The novel apoE mimetic peptide hEp demonstrates significant anti-atherosclerotic effects in a mouse model.
• hEp reduces atherosclerosis by enhancing cholesterol clearance and exhibiting anti-inflammatory and anti-oxidative activities.
• hEp holds promise as a potential therapeutic agent for atherosclerosis-related cardiovascular diseases.