Publication Date:
2003-04-12
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boucher, Philippe -- Gotthardt, Michael -- Li, Wei-Ping -- Anderson, Richard G W -- Herz, Joachim -- GM 52016/GM/NIGMS NIH HHS/ -- HL20948/HL/NHLBI NIH HHS/ -- HL63762/HL/NHLBI NIH HHS/ -- NS43408/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2003 Apr 11;300(5617):329-32.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9046, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12690199" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Aorta/cytology/metabolism/*pathology
;
Arteriosclerosis/*pathology/physiopathology/*prevention & control
;
Benzamides
;
Cattle
;
Cell Division
;
Cell Line
;
Cholesterol, Dietary/administration & dosage
;
Diet, Atherogenic
;
Elastin/analysis
;
Enzyme Inhibitors/pharmacology
;
Imatinib Mesylate
;
Ligands
;
Low Density Lipoprotein Receptor-Related
;
Protein-1/genetics/metabolism/*physiology
;
Mesenteric Arteries/cytology/pathology
;
Mice
;
Mice, Knockout
;
Mice, Transgenic
;
Muscle, Smooth, Vascular/cytology/*metabolism/pathology
;
Myocytes, Smooth Muscle/*metabolism/physiology
;
Phosphorylation
;
Piperazines/pharmacology
;
Platelet-Derived Growth Factor/metabolism/pharmacology
;
Proto-Oncogene Proteins c-sis
;
Pyrimidines/pharmacology
;
Receptor, Platelet-Derived Growth Factor beta/metabolism
;
Signal Transduction
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
