TY - JOUR
T1 - Plaque-penetrating peptide inhibits development of hypoxic atherosclerotic plaque
AU - She, Zhi Gang
AU - Hamzah, Juliana
AU - Kotamraju, Venkata R.
AU - Pang, Hong Bo
AU - Jansen, Shirley
AU - Ruoslahti, Erkki
N1 - Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2016/9/28
Y1 - 2016/9/28
N2 - 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.
AB - 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.
KW - Arterial occlusion
KW - Endothelium
KW - Plaque-associated macrophages
KW - Tumor-homing peptide
KW - p32/p33/gC1qR/HABP
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U2 - 10.1016/j.jconrel.2016.07.020
DO - 10.1016/j.jconrel.2016.07.020
M3 - Article
C2 - 27423327
AN - SCOPUS:84980009719
SN - 0168-3659
VL - 238
SP - 212
EP - 220
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -