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September 8, 2009PLoS ONEOpen Access

LRP1 Regulates Architecture of the Vascular Wall by Controlling PDGFRβ-Dependent Phosphatidylinositol 3-Kinase Activation

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Key result

Ablation of PI3K binding to PDGFRb significantly reduced spontaneous atherosclerosis and restored normal actin organization and smooth muscle cell migration in LRP1-deficient mice.

Population

Smooth muscle-specific LRP1 knockout mice and LRP1-deficient vascular smooth muscle cells

Comparison

Mutation of tyrosine 739/750 of PDGFRbeta to… vs smLRP1-/- mice expressing wild type PDGFR

Design

Preclinical

Authors

LZLi ZhouNorth Sichuan Medical UniversityYTYoshiharu TakayamaNational Agriculture and Food Research OrganizationPBPhilippe BoucherInserm

Discussion

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Implication

Extends PDGFRβ-PI3K mechanistic insights in LRP1 models; hypothesis-generating and should not yet change clinical practice.

Structured PICO

P
Population
Genetically modified mice (smLRP1-/-, LDLR-/-, PDGFRb F2/F2) used to study the role of LRP1 and PDGFRb-dependent PI3K activation in vascular wall architecture and atherosclerosis.
I
Intervention
Mutation of tyrosine 739/750 of PDGFRbeta to phenylalanines (PDGFRbeta F2/F2)
C
Comparator
smLRP1-/- mice expressing wild type PDGFR
O
Outcome
Spontaneous atherosclerosis, actin organization, and cell migrationsurrogate

LRP1 regulates actin organization and cell migration by controlling PDGFRbeta-dependent activation of PI3K, which is essential for maintaining vascular integrity and preventing atherosclerosis and Marfan syndrome-like phenotypes.

Limitations

  • Although PI3K is the only known cellular signal transducer that interacts with pY739 and 750 of PDGFRb, this does not exclude the possibility that another unknown signal modulator also interacts with this site and contributes to the pathogenic mechanism.

Cite This Study

Zhou et al. (2009) studied Atherosclerosis and Marfan syndrome-like vascular phenotypes. PDGFRb F2/F2 mutation (ablation of PI3K binding to PDGFRb) vs. smLRP1-/- mice expressing wild type PDGFRb was evaluated on Spontaneous atherosclerosis and smooth muscle cell migration. Ablation of PI3K binding to PDGFRb significantly reduced spontaneous atherosclerosis and restored normal actin organization and smooth muscle cell migration in LRP1-deficient mice.

synapsesocial.com/papers/6a6f59dffe4101aa97dfc241https://doi.org/10.1371/journal.pone.0006922
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1LRP1 Functions as an Atheroprotective Integrator of TGFβ and PDGF Signals in the Vascular Wall: Implications for Marfan Syndrome2007 · 128 citations
  2. 2Clearance of chylomicron remnants by the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor1991 · 211 citations
  3. 3Losartan, an AT1 Antagonist, Prevents Aortic Aneurysm in a Mouse Model of Marfan Syndrome2006 · 1,812 citations
  4. 4Insulin-like growth factor-I and platelet-derived growth factor-BB induce directed migration of human arterial smooth muscle cells via signaling pathways that are distinct from those of proliferation.1994 · 412 citations
  5. 5LRP: a multifunctional scavenger and signaling receptor2001 · 966 citations