Plaque-penetrating peptide inhibits development of hypoxic atherosclerotic plaque

Z.G. She, Juliana Hamzah, V.R. Kotamraju, H.B. Pang, S. Jansen, E. Ruoslahti

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

© 2016 Elsevier B.V.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.
Original languageEnglish
Pages (from-to)212-220
JournalJournal of Controlled Release
Volume238
DOIs
Publication statusPublished - 2016

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Atherosclerotic Plaques
Atherosclerosis
Peptides
Macrophages
Apoptosis
Apolipoproteins E
Lipid Metabolism
Pharmaceutical Preparations
Neoplasms

Cite this

She, Z.G. ; Hamzah, Juliana ; Kotamraju, V.R. ; Pang, H.B. ; Jansen, S. ; Ruoslahti, E. / Plaque-penetrating peptide inhibits development of hypoxic atherosclerotic plaque. In: Journal of Controlled Release. 2016 ; Vol. 238. pp. 212-220.
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Plaque-penetrating peptide inhibits development of hypoxic atherosclerotic plaque. / She, Z.G.; Hamzah, Juliana; Kotamraju, V.R.; Pang, H.B.; Jansen, S.; Ruoslahti, E.

In: Journal of Controlled Release, Vol. 238, 2016, p. 212-220.

Research output: Contribution to journalArticle

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AU - She, Z.G.

AU - Hamzah, Juliana

AU - Kotamraju, V.R.

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AU - Jansen, S.

AU - Ruoslahti, E.

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AB - © 2016 Elsevier B.V.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.

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