LRP: Role in Vascular Wall Integrity and Protection from Atherosclerosis

@article{Boucher2003LRPRI,
  title={LRP: Role in Vascular Wall Integrity and Protection from Atherosclerosis},
  author={Philippe Boucher and Michael Gotthardt and Wei-ping Li and Richard G. W. Anderson and Joachim Herz},
  journal={Science},
  year={2003},
  volume={300},
  pages={329 - 332}
}
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… 
Thymosin β4 preserves vascular smooth muscle phenotype in atherosclerosis via regulation of Low Density Lipoprotein Related Protein 1 (LRP1)
Atherosclerosis is a progressive, degenerative vascular disease and a leading cause of morbidity and mortality. In response to endothelial damage, platelet derived growth factor (PDGF)-BB induced
LRP1 Regulates Architecture of the Vascular Wall by Controlling PDGFRβ-Dependent Phosphatidylinositol 3-Kinase Activation
TLDR
The data suggest that LRP1 regulates actin organization and cell migration by controlling PDGFRβ-dependent activation of PI3K, which is essential for maintaining vascular integrity, and for the prevention of atherosclerosis as well as Marfan syndrome.
Thymosin β4 mediates vascular protection via regulation of Low Density Lipoprotein Related Protein 1 (LRP1)
TLDR
This study identifies Tβ4 as a key regulator of LRP1 for maintaining vascular health, providing insight which may reveal useful therapeutic targets for modulation of VSMC phenotypic switching and disease progression.
Ang II-stimulated migration of vascular smooth muscle cells is dependent on LR11 in mice.
TLDR
It is shown that circulating sLR11 is a novel marker of carotid intima-media thickness (IMT) and that targeted disruption of the LR11 gene greatly reduces intimal thickening of arteries through attenuation of Ang II-induced migration of SMCs.
LRP1 promotes synthetic phenotype of pulmonary artery smooth muscle cells in pulmonary hypertension.
TLDR
The results indicate that LRP1 promotes the dedifferentiation of PASMC from a contractile to a synthetic phenotype thus suggesting its contribution to vascular remodeling in PH.
PDGFRβ signaling regulates local inflammation and synergizes with hypercholesterolemia to promote atherosclerosis
TLDR
It is demonstrated that PDGFRβ pathway activation has a profound effect on vascular disease and support the conclusion that inflammation in the outer arterial layers is a driving process for atherosclerosis.
PDGF and cardiovascular disease.
  • E. Raines
  • Biology, Medicine
    Cytokine & growth factor reviews
  • 2004
TLDR
Different genetic manipulations in vascular cells combined with various inhibitory strategies have provided strong evidence for PDGF playing a prominent role in the migration of SMC into the neointima following acute injury and in atherosclerosis.
LRP1B is a negative modulator of increased migration activity of intimal smooth muscle cells from rabbit aortic plaques.
TLDR
Results indicate that LRP1B regulated the migration activity of SMCs through the modulation of PDGF beta-receptor-mediated pathway.
Macrophage LRP1 Suppresses Neo-Intima Formation during Vascular Remodeling by Modulating the TGF-β Signaling Pathway
TLDR
The data demonstrate that macrophage LRP1 protects the vasculature by limiting remodeling events associated with flow by modulating both the expression and protein levels of TGF-β2 in macrophages.
LRP1 Protects the Vasculature by Regulating Levels of Connective Tissue Growth Factor and HtrA1
TLDR
2 new molecules are highlighted, connective tissue growth factor and HtrA1, which contribute to detrimental changes in the vasculature and, therefore, represent new target molecules for potential therapeutic intervention to maintain vessel wall homeostasis.
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