LRP: Role in vascular wall integrity and protection from atherosclerosis

Philippe Boucher, Michael Gotthardt, Wei Ping Li, Richard G W Anderson, Joachim Herz

Research output: Contribution to journalArticle

396 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)329-332
Number of pages4
JournalScience
Volume300
Issue number5617
DOIs
StatePublished - Apr 11 2003

ASJC Scopus subject areas

  • General

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    Boucher, P., Gotthardt, M., Li, W. P., Anderson, R. G. W., & Herz, J. (2003). LRP: Role in vascular wall integrity and protection from atherosclerosis. Science, 300(5617), 329-332. https://doi.org/10.1126/science.1082095