Evidence map›Paper›PMID 25824691›Full record

ReviewBlood2015

Activated protein C: biased for translation.

John H Griffin, Berislav V Zlokovic, Laurent O Mosnier

Open access · bronzeAbstract readReview
In one paragraph

Review in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers.

0numbers the graph read from it
0cells of the map it votes in
171citing papers in PubMed
19.4field-weighted citation impact, top 1% 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

171 citing papers in PubMed, 256 citations in OpenAlex.

  1. Trial
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  5. Achieving protease substrate-specific inhibition by mAb dual functional selections.Protein science : a publication of the Protein Society · 2026
    Article
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111 more citing papers are in PubMed but not listed here.

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

3 authors at 2 institutions in 1 country.

John H GriffinDepartment of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA; Division of Hematology-Oncology, Department of Medicine, University of California, San Diego, San Diego, CA; and.
Berislav V ZlokovicZilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Laurent O MosnierDepartment of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA;
Scripps Research Institute · USUniversity of Southern California · US

Funding

THROMBUS FORMATION IN BABOONSP01HL031950 · NHLBI · SCRIPPS RESEARCH INSTITUTE, THE · PI GRIFFIN, JOHN H · 1985 to 2015
$29.4M
Structure and Function of Protein CR01HL052246 · NHLBI · SCRIPPS RESEARCH INSTITUTE, THE · PI GRIFFIN, JOHN H · 2005 to 2017
$9.6M
REGULATION OF BRAIN THROMBOSIS IN STROKE MODELSR01HL063290 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ZLOKOVIC, BERISLAV V · 1999 to 2013
$7.5M
Structure-function of cytoprotective coagulation proteases and their receptorsR01HL104165 · NHLBI · SCRIPPS RESEARCH INSTITUTE, THE · PI MOSNIER, LAURENT OLIVIER · 2011 to 2024
$6.1M
STRUCTURE/FUNCTION OF PROTEIN CR37HL052246 · NHLBI · SCRIPPS RESEARCH INSTITUTE · PI GRIFFIN, JOHN H · 1995 to 2004
$2.9M
NHLBI NIH HHS HL031950NHLBI NIH HHS HL052246NHLBI NIH HHS HL063290NHLBI NIH HHS HL104165NHLBI NIH HHS P01 HL031950NHLBI NIH HHS R01 HL052246NHLBI NIH HHS R01 HL063290NHLBI NIH HHS R01 HL104165NHLBI NIH HHS R37 HL052246
6 · The paper itself

Abstract

The homeostatic blood protease, activated protein C (APC), can function as (1) an antithrombotic on the basis of inactivation of clotting factors Va and VIIIa; (2) a cytoprotective on the basis of endothelial barrier stabilization and anti-inflammatory and antiapoptotic actions; and (3) a regenerative on the basis of stimulation of neurogenesis, angiogenesis, and wound healing. Pharmacologic therapies using recombinant human and murine APCs indicate that APC provides effective acute or chronic therapies for a strikingly diverse range of preclinical injury models. APC reduces the damage caused by the following: ischemia/reperfusion in brain, heart, and kidney; pulmonary, kidney, and gastrointestinal inflammation; sepsis; Ebola virus; diabetes; and total lethal body radiation. For these beneficial effects, APC alters cell signaling networks and gene expression profiles by activating protease-activated receptors 1 and 3. APC's activation of these G protein-coupled receptors differs completely from thrombin's activation mechanism due to biased signaling via either G proteins or β-arrestin-2. To reduce APC-associated bleeding risk, APC variants were engineered to lack >90% anticoagulant activity but retain normal cell signaling. Such a neuroprotective variant, 3K3A-APC (Lys191-193Ala), has advanced to clinical trials for ischemic stroke. A rich data set of preclinical knowledge provides a solid foundation for potential translation of APC variants to future novel therapies.

Indexed as

CytoprotectionAnimalsAnticoagulantsHumansProtein CAnticoagulantsProtein C

Identifiers

PMID25824691
PMCPMC4424414
OpenAlexW2092338209

What OpenQuestion holds

Textmetadata
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.