TY - JOUR
T1 - LRP
T2 - Role in vascular wall integrity and protection from atherosclerosis
AU - Boucher, Philippe
AU - Gotthardt, Michael
AU - Li, Wei Ping
AU - Anderson, Richard G W
AU - Herz, Joachim
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003/4/11
Y1 - 2003/4/11
N2 - Vascular smooth muscle cell (SMC) proliferation and migration are important events in the development of atherosclerosis. The low-density lipoprotein receptor-related protein (LRP1) mediates suppression of SMC migration induced by platelet-derived growth factor (PDGF). Here we show that LRP1 forms a complex with the PDGF receptor (PDGFR). Inactivation of LRP1 in vascular SMCs of mice causes PDGFR overexpression and abnormal activation of PDGFR signaling, resulting in disruption of the elastic layer, SMC proliferation, aneurysm formation, and marked susceptibility to cholesterol-induced atherosclerosis. The development of these abnormalities was reduced by treatment with Gleevec, an inhibitor of PDGF signaling. Thus, LRP1 has a pivotal role in protecting vascular wall integrity and preventing atherosclerosis by controlling PDGFR activation.
AB - Vascular smooth muscle cell (SMC) proliferation and migration are important events in the development of atherosclerosis. The low-density lipoprotein receptor-related protein (LRP1) mediates suppression of SMC migration induced by platelet-derived growth factor (PDGF). Here we show that LRP1 forms a complex with the PDGF receptor (PDGFR). Inactivation of LRP1 in vascular SMCs of mice causes PDGFR overexpression and abnormal activation of PDGFR signaling, resulting in disruption of the elastic layer, SMC proliferation, aneurysm formation, and marked susceptibility to cholesterol-induced atherosclerosis. The development of these abnormalities was reduced by treatment with Gleevec, an inhibitor of PDGF signaling. Thus, LRP1 has a pivotal role in protecting vascular wall integrity and preventing atherosclerosis by controlling PDGFR activation.
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U2 - 10.1126/science.1082095
DO - 10.1126/science.1082095
M3 - Article
C2 - 12690199
AN - SCOPUS:0037432766
SN - 0036-8075
VL - 300
SP - 329
EP - 332
JO - Science
JF - Science
IS - 5617
ER -