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Publication : LRP: role in vascular wall integrity and protection from atherosclerosis.

First Author  Boucher P Year  2003
Journal  Science Volume  300
Issue  5617 Pages  329-32
PubMed ID  12690199 Mgi Jnum  J:82871
Mgi Id  MGI:2655891 Doi  10.1126/science.1082095
Citation  Boucher P, et al. (2003) LRP: role in vascular wall integrity and protection from atherosclerosis. Science 300(5617):329-32
abstractText  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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