Evidence map›Paper›PMID 29367646›Full record

ArticleScientific reports2018

Vascular endothelial effects of collaborative binding to platelet/endothelial cell adhesion molecule-1 (PECAM-1).

Raisa Yu Kiseleva, C F Greineder, C H Villa, O A Marcos-Contreras, E D Hood, V V Shuvaev, H M DeLisser, V R Muzykantov

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.4field-weighted citation impact, top 21% of its field
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

9 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Overcoming Vascular Barriers to Improve the Theranostic Outcomes of Nanomedicines.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022
    Review
  7. Bivalent engagement of endothelial surface antigens is critical to prolonged surface targeting and protein delivery in vivo.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
    Article
  8. Selective targeting of nanomedicine to inflamed cerebral vasculature to enhance the blood-brain barrier.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  9. Article
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

8 authors at 1 institution in 1 country.

Raisa Yu KiselevaDepartment of Pharmacology and Center for Translational Targeted Therapeutics and Nanomedicine of the Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, United States of America.ORCID http://orcid.org/0000-0001-8065-3551
C F GreinederDepartment of Pharmacology and Center for Translational Targeted Therapeutics and Nanomedicine of the Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, United States of America. cgreineder@gmail.com.
C H VillaDepartment of Pharmacology and Center for Translational Targeted Therapeutics and Nanomedicine of the Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, United States of America.
O A Marcos-ContrerasDepartment of Pharmacology and Center for Translational Targeted Therapeutics and Nanomedicine of the Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, United States of America.
E D HoodDepartment of Pharmacology and Center for Translational Targeted Therapeutics and Nanomedicine of the Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, United States of America.
V V ShuvaevDepartment of Pharmacology and Center for Translational Targeted Therapeutics and Nanomedicine of the Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, United States of America.
H M DeLisserDepartment of Pharmacology and Center for Translational Targeted Therapeutics and Nanomedicine of the Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, United States of America.
V R MuzykantovDepartment of Pharmacology and Center for Translational Targeted Therapeutics and Nanomedicine of the Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, United States of America. muzykantov@pennmedicine.upenn.edu.
Target (United States) · US

Funding

TRAINING GRANT IN HEMOSTASIS AND THROMBOSIST32HL007971 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Rodney M Camire · 2001 to 2026
$10.6M
TRANSFUSION MEDICINE RESEARCH TRAINING PROGRAMT32HL007775 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI SIEGEL, DONALD LAWRENCE · 1993 to 2023
$2.8M
Targeting novel biotherapeutics to endotheliumR01HL128398 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2015 to 2018
$2.2M
Endothelial targeting of antioxidantsR01HL126874 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2016 to 2019
$1.7M
ICAM-1 targeted thrombomodulin: an experimental therapeutic for the Acute Respiratory Distress SyndromeK08HL130430 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI GREINEDER, COLIN FRED · 2016 to 2020
$665k
NHLBI NIH HHS K08 HL130430NHLBI NIH HHS R01 HL126874NHLBI NIH HHS R01 HL128398NHLBI NIH HHS T32 HL007775NHLBI NIH HHS T32 HL007971
6 · The paper itself

Abstract

Targeting drugs to endothelial cells has shown the ability to improve outcomes in animal models of inflammatory, ischemic and thrombotic diseases. Previous studies have revealed that certain pairs of ligands (antibodies and antibody fragments) specific for adjacent, but distinct, epitopes on PECAM-1 enhance each other's binding, a phenomenon dubbed Collaborative Enhancement of Paired Affinity Ligands, or CEPAL. This discovery has been leveraged to enable simultaneous delivery of multiple therapeutics to the vascular endothelium. Given the known role of PECAM-1 in promoting endothelial quiescence and cell junction integrity, we sought here to determine if CEPAL might induce unintended vascular effects. Using a combination of in vitro and in vivo techniques and employing human and mouse endothelial cells under physiologic and pathologic conditions, we found only modest or non-significant effects in response to antibodies to PECAM-1, whether given solo or in pairs. In contrast, these methods detected significant elevation of endothelial permeability, pro-inflammatory vascular activation, and systemic cytokine release following antibody binding to the related endothelial junction protein, VE-Cadherin. These studies support the notion that PECAM-1-targeted CEPAL provides relatively well-tolerated endothelial drug delivery. Additionally, the analysis herein creates a template to evaluate potential toxicities of vascular-targeted nanoparticles and protein therapeutics.

Indexed as

AnimalsAntibodiesAntigens, CDCadherin 5CadherinsCells, CulturedCytokinesEndothelial CellsHumansMice, Inbred C57BLPermeabilityPlatelet Endothelial Cell Adhesion Molecule-1Protein BindingAntibodiesAntigens, CDCadherin 5CadherinsCytokinesPlatelet Endothelial Cell Adhesion Molecule-1

Identifiers

PMID29367646
PMCPMC5784113
OpenAlexW2807526539

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.