Evidence map›Paper›PMID 42662070›Full record

ArticleBlood vessels, thrombosis & hemostasis2026

Nascent ADAM17 synthesis potentiates GPIbα cleavage in resting and stimulated stored platelets.

Shayan Askari, Harriet Ghansah, Christopher D Mansi, Timothy J Stalker, Lawrence E Goldfinger

Abstract read
In one paragraph

Article in Blood vessels, thrombosis & hemostasis, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

5 authors.

Shayan AskariCardeza Foundation for Hematologic Research, Division of Hematology, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA.
Harriet GhansahCardeza Foundation for Hematologic Research, Division of Hematology, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA.
Christopher D MansiCardeza Foundation for Hematologic Research, Division of Hematology, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA.
Timothy J StalkerCardeza Foundation for Hematologic Research, Division of Hematology, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA.
Lawrence E GoldfingerCardeza Foundation for Hematologic Research, Division of Hematology, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA.

Funding

Function and regulation of constitutive protein translation in plateletsR01HL159006 · NHLBI · THOMAS JEFFERSON UNIVERSITY · PI GOLDFINGER, LAWRENCE E · 2021 to 2024
$1.6M
Short inhibitory RNAs in platelet and megakaryocyte functionR01HL172942 · NHLBI · THOMAS JEFFERSON UNIVERSITY · PI Lawrence E Goldfinger · 2025 to 2026
$1.1M
RNA-based therapeutics for hemostasis and thrombosisR33HL173910 · NHLBI · THOMAS JEFFERSON UNIVERSITY · PI GOLDFINGER, LAWRENCE E, STALKER, TIMOTHY J. · 2024 to 2025
$1.1M
NHLBI NIH HHS R01 HL159006NHLBI NIH HHS R01 HL172942NHLBI NIH HHS R33 HL173910
6 · The paper itself

Abstract

Platelet concentrates stored at room temperature have a shelf life of 5 to 7 days. During storage, platelets undergo glycoprotein cleavage by metalloproteases, notably cleavage of glycoprotein Ibα (GPIbα) by a disintegrin and metalloprotease 17 (ADAM17), which leads to decreased posttransfusion reactivity and recovery. To investigate the putative roles of nascent synthesis of ADAM17 in GPIbα shedding and platelet function during room temperature platelet storage. Human platelets maintained in autologous plasma were treated with naked endonuclease-resistant ADAM17 or control short inhibitory RNA (siRNA) and monitored for molecular and cellular effects during storage. Platelet-specific Adam17-deleted mice were generated, and the dynamics of GPIbα cleavage were assessed. Platelets translated nascent ADAM17 during storage, coinciding with progressive GPIbα ectodomain cleavage. siRNA treatment suppressed ADAM17 translation and rescued total but not surface levels of full-length GPIbα in resting platelets during storage. Flow cytometry and confocal microscopy in permeabilized platelets indicated an internal pool of GPIbα protected from agonist-induced cleavage by cell-permeable ADAM17 pharmacological blockade but not by non-cell-permeable blocking antibodies. ADAM17 siRNA did not alter stimulation-mediated decrease in surface GPIbα across 5 days in storage. Deletion of murine platelet Adam17 resulted in increased basal GpIbα in an inverse gene-dose-dependent manner, and protection from stimulation-mediated cleavage. Hemostasis was normal in platelet-specific Adam17-deleted mice. ADAM17 synthesis contributes to GPIbα cleavage in stored platelets, but extant siRNA-resistant ADAM17 is sufficient to cleave GPIbα upon platelet stimulation. An internal pool of GPIbα is exposed upon platelet stimulation but subject to rapid cleavage by ADAM17.

Identifiers

PMID42662070
PMCPMC13519630

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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.