Human Oxidation-Specific Antibodies Reduce Foam Cell Formation and Atherosclerosis Progression
Key result
Plasma IK17-scFv expression cuts en face atherosclerosis ~46% in hypercholesterolemic mice.
- 46% reduction
- P<0.001
Why the study?
The in vivo importance of scavenger receptor-mediated uptake of oxidized LDL in atherogenesis and the efficacy of oxidation-specific antibodies to inhibit atherosclerosis progression were uncertain.
Does human oxidation-specific antibody IK17 reduce atherosclerosis progression in cholesterol-fed LDLR−/− and LDLR−/−/Rag−/− mice?
Population
Cholesterol-fed LDLR−/− and LDLR−/−/Rag−/− mice
Comparison
IK17-Fab or IK17-scFv treatment vs PBS or control adenoviral-EGFP vector
Design
In vivo experimental study with antibody infusion and adenoviral vector administration
Follow-up
14 to 16 weeks
Authors
Discussion
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Member takes
Implication
Oxidation-specific antibodies targeting oxidized LDL reduce atherosclerosis progression in mouse models, suggesting a potential therapeutic pathway for cardiovascular disease.
Key Points
- To assess the in vivo importance of scavenger receptor-mediated oxidized low-density lipoprotein uptake and evaluate the efficacy of human antibody fragments IK17-Fab and IK17-scFv in inhibiting atherosclerosis.
- Cholesterol-fed LDLR−/− mice received intraperitoneal injections of human IK17-Fab (2.5 mg/kg) three times weekly for 14 weeks.
- Immunodeficient LDLR−/−/Rag−/− mice were treated with an adenoviral vector encoding IK17-scFv (Adv-IK17-scFv) or control vector (Adv-EGFP) intravenously every two weeks for 16 weeks.
- IK17-Fab sustained circulating antibody levels for 8 weeks before murine anti-human antibodies emerged, achieving a 29% decrease in en face atherosclerosis versus PBS after 14 weeks.
- Adv-IK17-scFv generated sustained plasma levels and reduced en face atherosclerosis by 46% (P < 0.001) compared with Adv-EGFP in LDLR−/−/Rag−/− mice.
- Peritoneal macrophages harvested from mice receiving Adv-IK17-scFv exhibited markedly reduced intracellular lipid accumulation relative to control mice.
Structured PICO
Does human oxidation-specific antibody IK17 reduce atherosclerosis progression in cholesterol-fed LDLR−/− and LDLR−/−/Rag−/− mice?
P
Population
Cholesterol-fed LDLR-/- mice and LDLR-/-/Rag-/- mice treated for 14 to 16 weeks.
I
Intervention
Intraperitoneal infusion of human IK17-Fab (2.5mg/kg) 3 times/week for 14 weeks (in LDLR−/− mice) or adenoviral vector encoding Adv-IK17-scFv intravenously every 2 weeks for 16 weeks (in LDLR−/−/Rag−/− mice)
C
Comparator
PBS (for LDLR−/− mice) or control adenoviral-enhanced green fluorescent protein (adv-EGFP) vector (for LDLR−/−/Rag−/− mice)
O
Outcome
En face atherosclerosissurrogate
Main Result
Effect estimate: 46% reduction
p-value: p=<0.001
Oxidation-specific antibodies targeting oxidized LDL reduce atherosclerosis progression in mouse models, suggesting a potential therapeutic pathway for cardiovascular disease.
Cite This Study
Tsimikas et al. (2011) studied Atherosclerosis. Human antibody IK17-Fab or IK17-scFv vs. PBS or control adenoviral-enhanced green fluorescent protein (adv-EGFP) vector was evaluated on en face atherosclerosis (46% reduction, p=<0.001). In LDLR-/-/Rag-/- mice, sustained levels of plasma IK17-scFv led to a 46% reduction in en face atherosclerosis compared to adv-EGFP (P<0.001).