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Updated: Mar 17, 2026
Synthesis of Monocyte-targeting Peptide Amphiphile Micelles for Imaging of Atherosclerosis
Published on: November 17, 2017
Plaque-penetrating peptide inhibits development of hypoxic atherosclerotic plaque
Zhi-Gang She1, Juliana Hamzah2, Venkata R Kotamraju1
1Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, 92037, CA, USA.
Abstract:
Atherosclerosis treatments are generally aimed at altering systemic lipid metabolism such that atherogenesis, the formation of plaque, is curtailed. The plaques themselves offer some potential therapeutic targets. For example, selective depletion of macrophages, which play a key role in atherogenesis, inhibits plaque formation. However, it has not been possible to take advantage of these targets because the drugs that have been tested have not been sufficiently selective. We have developed a peptide, LyP-1, which specifically targets atherosclerotic plaques, penetrates into plaque interior, and accumulates in plaque macrophages. In tumors, LyP-1 can cause apoptosis in cells that take up the peptide. Here we show, using three different atherosclerosis models in ApoE null mice that prolonged systemic treatment with LyP-1 triggers apoptosis of plaque macrophages and reduces plaque in advanced hypoxic plaques, and that it does so without increasing necrotic core of plaques or causing detectable side effects. We also show that LyP-1 recognizes human plaque. These findings suggest that LyP-1 could serve as a lead compound for the development of a new class of anti-atherosclerosis drugs.
Insights
A novel peptide, LyP-1, effectively targets and reduces atherosclerotic plaques by inducing apoptosis in plaque macrophages. This peptide shows promise as a new therapeutic strategy for atherosclerosis without significant side effects.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Drug Discovery
Background:
- Atherosclerosis treatments focus on lipid metabolism, but plaque-specific targets like macrophages remain challenging.
- Existing drugs lack the selectivity needed to target macrophages within atherosclerotic plaques.
- Macrophages are crucial in atherogenesis and represent a potential therapeutic target.
Purpose of the Study:
- To evaluate the therapeutic potential of the peptide LyP-1 in atherosclerosis.
- To determine if LyP-1 can selectively target and reduce atherosclerotic plaque burden.
- To assess LyP-1's safety and efficacy in preclinical models.
Main Methods:
- Developed and utilized the peptide LyP-1, known to target tumors.
- Administered LyP-1 systemically to ApoE null mice across three atherosclerosis models.
- Assessed plaque macrophage apoptosis, plaque size, necrotic core, and potential side effects.
- Validated LyP-1's recognition of human atherosclerotic plaques.
Main Results:
- LyP-1 treatment led to apoptosis of macrophages within atherosclerotic plaques.
- Significant reduction in plaque size was observed in advanced, hypoxic plaques.
- No increase in necrotic core or detectable side effects were noted.
- LyP-1 demonstrated recognition of human atherosclerotic plaques.
Conclusions:
- LyP-1 selectively targets atherosclerotic plaques and macrophages, reducing plaque burden.
- LyP-1 offers a potential new therapeutic approach for atherosclerosis.
- Further development of LyP-1 could lead to a novel class of anti-atherosclerosis drugs.
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