Evidence map›Paper›PMID 18182571›Full record

ArticleBlood2008

RhoA activation and actin reorganization involved in endothelial CAM-mediated endocytosis of anti-PECAM carriers: critical role for tyrosine 686 in the cytoplasmic tail of PECAM-1.

Carmen Garnacho, Vladimir Shuvaev, Anu Thomas, Lindsay McKenna, Jing Sun, Michael Koval, Steven Albelda, Vladimir Muzykantov, Silvia Muro

Abstract read
In one paragraph

Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed.

  1. Endothelial-Specific Targeting of RhoA Signaling via CD31 Antibody-Conjugated Nanoparticles.The Journal of pharmacology and experimental therapeutics · 2023
    Article
  2. Review
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  5. Review
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  7. Macrophage/monocyte-specific deletion of Ras homolog gene family member A (RhoA) downregulates fractalkine receptor and inhibits chronic rejection of mouse cardiac allografts.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2017
    Article
  8. Article
  9. PECAM-1 isoforms, eNOS and endoglin axis in regulation of angiogenesis.Clinical science (London, England : 1979) · 2015
    Review
  10. Flow shear stress differentially regulates endothelial uptake of nanocarriers targeted to distinct epitopes of PECAM-1.Journal of controlled release : official journal of the Controlled Release Society · 2015
    Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Carmen GarnachoDepartment of Pharmacology, School of Medicine, University of Pennsylvania, Philadelphia 19104-6068, USA.
Vladimir Shuvaev
Anu Thomas
Lindsay McKenna
Jing Sun
Michael Koval
Steven Albelda
Vladimir Muzykantov
Silvia Muro

Funding

Vector CoreP30DK047757 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI CALCEDO, ROBERTO · 1993 to 2017
$18.0M
Targeting Carriers with Controlled Geometry to EndotheliumR01HL087036 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2008 to 2012
$2.0M
Augmentation of Antioxidant Defenses by ImmunotargetingR01HL073940 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2004 to 2007
$1.6M
Targeting of Drugs to ICAMR01HL071175 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2002 to 2005
$1.4M
Nanocarriers for delivery of antioxidants to endotheliumR01HL078785 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2004 to 2004
$396k
Targeted enzyme delivery systems treatment niemann-pickR21HL085533 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MURO GALINDO, SILVIA · 2006 to 2007
$387k
NHLBI NIH HHS HL078785NHLBI NIH HHS HL73940NHLBI NIH HHS R01 HL071175NHLBI NIH HHS R01 HL073940NHLBI NIH HHS R01 HL078785NHLBI NIH HHS R01 HL087036NHLBI NIH HHS R01 HL71175NHLBI NIH HHS R21 HL085533NHLBI NIH HHS R21 HL85533NIDDK NIH HHS P30 DK047757NIDDK NIH HHS P30 DK47757-14
6 · The paper itself

Abstract

Platelet-endothelial cell adhesion molecule-1 (PECAM-1), a transmembrane glycoprotein involved in leukocyte transmigration, represents a good target for endothelial drug delivery (eg, using antibody-directed nanocarriers, anti-PECAM/NCs). Although endothelial cells do not internalize PECAM antibodies, PECAM-1 engagement by multivalent anti-PECAM conjugates and nanocarriers causes endocytosis via a nonclassic CAM-mediated pathway. We found that endothelial uptake of multivalent anti-PECAM complexes is associated with PECAM-1 phosphorylation. Using model REN cells expressing a series of PECAM-1 deletion and point mutants, we found that the PECAM-1 cytoplasmic domain and, more precisely, PECAM-1 tyrosine 686, is critical in mediating RhoA activation and recruitment of EGFP-RhoA to anti-PECAM/NC binding sites at the plasmalemma, actin polymerization into phalloidin-positive stress fibers, and finally CAM endocytosis of anti-PECAM/NCs. Endothelial targeting and endocytosis of anti-PECAM/NCs were markedly efficient and did not compromise endothelial barrier function in vitro (determined by immunostaining of VE-cadherin and (125)I-albumin transport across endothelial monolayers) or in vivo (determined by electron microscopy imaging of pulmonary capillaries and (125)I-albumin transport from the blood into the lung tissue after intravenous injection of anti-PECAM/NCs in mice). These results reveal PECAM-1 signaling and interactions with the cytoskeleton, which are required for CAM-endocytosis, and may provide safe intra-endothelial drug delivery by anti-PECAM/NCs.

Indexed as

EndocytosisActinsAnimalsAntibodiesCells, CulturedCytoplasmEndothelial CellsEnzyme ActivationHumansMaleMiceMice, Inbred C57BLPhosphorylationPlatelet Endothelial Cell Adhesion Molecule-1rhoA GTP-Binding ProteinTyrosineActinsAntibodiesPlatelet Endothelial Cell Adhesion Molecule-1rhoA GTP-Binding ProteinTyrosine

Identifiers

PMID18182571
PMCPMC2265450

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.