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LRP: Role in Vascular Wall Integrity and Protection from Atherosclerosis
Philippe Boucher,1*Michael Gotthardt,1*Wei-Ping Li,2Richard G. W. Anderson,2Joachim Herz1
Vascular smooth muscle cell (SMC) proliferation and
migration are important events in the development of atherosclerosis.The low-density lipoprotein receptor-related protein (LRP1) mediatessuppression of SMC migration induced by platelet-derived growthfactor
(PDGF). Here we show that LRP1 forms a complex with thePDGF receptor
(PDGFR). Inactivation of LRP1 in vascular SMCs ofmice causes PDGFR
overexpression and abnormal activation of PDGFRsignaling, resulting in
disruption of the elastic layer, SMC proliferation,aneurysm formation,
and marked susceptibility to cholesterol-inducedatherosclerosis. The
development of these abnormalities was reducedby treatment with
Gleevec, an inhibitor of PDGF signaling. Thus,LRP1 has a pivotal role
in protecting vascular wall integrityand preventing atherosclerosis by
controlling PDGFR activation.
1 Department of Molecular Genetics,
2 Department of Cell Biology, University of Texas
Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX
75390-9046, USA.
*
These authors contributed equally to this work.
To whom correspondence should be addressed.
E-mail: Joachim.Herz{at}UTSouthwestern.edu
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Testing the role of apoA-I, HDL, and cholesterol efflux in the atheroprotective action of low-level apoE expression.
F. E. Thorngate, P. G. Yancey, G. Kellner-Weibel, L. L. Rudel, G. H. Rothblat, and D. L. Williams (2003)
J. Lipid Res.
44, 2331-2338
|Abstract »|Full Text »|PDF »
Modulation of the LDL receptor and LRP levels by HIV protease inhibitors.
H. Tran, S. Robinson, I. Mikhailenko, and D. K. Strickland (2003)
J. Lipid Res.
44, 1859-1869
|Abstract »|Full Text »|PDF »
Apolipoprotein E Binding to Low Density Lipoprotein Receptor-related Protein-1 Inhibits Cell Migration via Activation of cAMP-dependent Protein Kinase A.
