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Biological effects of cardiac magnetic resonance on human blood cells
Lancellotti P, Nchimi A, Delierneux C, Hego A, Gosset C, Gothot A, Jean-Flory Tshibanda L, Oury C.
Circulation Cardiovasc Imaging
.
2015;8
Cardiac magnetic resonance (CMR) is increasingly used for the diagnosis and management of cardiac diseases. Recent studies have
reported immediate post-CMR DNA double-strand breaks in T lymphocytes. We sought to evaluate CMR-induced DNA damage in
lymphocytes, alterations of blood cells, and their temporal persistence. In 20 prospectively enrolled healthy men (31.4±7.9 years),
blood was drawn before and after (1-2 hours, 2 days, 1 month, and 1 year) unenhanced 1.5T CMR. Blood cell counts, cell death, and
activation status of lymphocytes, monocytes, neutrophils, and platelets were evaluated. The first 2-hour post-CMR were characte-
rized by a small increase of lymphocyte B and neutrophil counts and a transient drop of total lymphocytes because of a decrease in
natural killer cells. Among blood cells, only neutrophils and monocytes displayed slight and transient activation. DNA double-strand
breaks in lymphocytes were quantified through flow cytometric analysis of H2AX phosphorylation (γ-H2AX). γ-H2AX intensity in
T lymphocytes did not change early after CMR but increased significantly at day 2 ≤1 month before returning to baseline levels of
1-year post-CMR. Unenhanced CMR is associated with minor but significant immediate blood cell alterations or activations figuring
inflammatory response, as well as DNA damage in T lymphocytes observed from day 2 until the first month but disappearing at
1-year follow-up. Although further studies are required to definitely state whether CMR can be used safely, our findings already call
for caution when it comes to repeat this examination within a month.
Dual-specificity phosphatase 3 deficiency or inhibition limits platelet activation and arterial thrombosis
Musumeci L, Kuijpers MJ, Gilio K, Hego A, Theatre E, Maurissen L, Vandereyken M, Diogo CV, Lecut C, Guilmain W, Bobkova EV, Eble
JA, Dahl R, Drion P, Rascon J, Mostofi Y, Yuan H, Sergienko E, Chung TD, Thiry M, Senis Y, Moutschen M, Mustelin T, Lancellotti P,
Heemskerk JW, Tautz L, Oury C*, Rahmouni S*. *these authors contributed equally to the work
Circulation.
2015;131:656-668
A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. A better
understanding of the molecular mechanisms leading to platelet activation is important for the development of improved therapies.
Recently, protein tyrosine phosphatases have emerged as critical regulators of platelet function. This is the first report implicating
the dual-specificity phosphatase 3 (DUSP3) in platelet signaling and thrombosis. This phosphatase is highly expressed in human
and mouse platelets. Platelets from DUSP3-deficient mice displayed a selective impairment of aggregation and granule secretion
mediated by the collagen receptor glycoprotein VI and the C-type lectin-like receptor 2. DUSP3-deficient mice were more resistant
to collagen- and epinephrine-induced thromboembolism compared with wild-type mice and showed severely impaired thrombus
formation on ferric chloride-induced carotid artery injury. Intriguingly, bleeding times were not altered in DUSP3-deficient mice. At
the molecular level, DUSP3 deficiency impaired Syk tyrosine phosphorylation, subsequently reducing phosphorylation of phospho-
lipase Cγ2 and calcium fluxes. To investigate DUSP3 function in human platelets, a novel small-molecule inhibitor of DUSP3 was
developed. This compound specifically inhibited collagen- and C-type lectin-like receptor 2-induced human platelet aggregation,
thereby phenocopying the effect of DUSP3 deficiency in murine cells. DUSP3 plays a selective and essential role in collagen- and
C-type lectin-like receptor 2-mediated platelet activation and thrombus formation in vivo. Inhibition of DUSP3 may prove therapeutic
for arterial thrombosis. This is the first time a protein tyrosine phosphatase, implicated in platelet signaling, has been targeted with
a small-molecule drug.
Awards
Patrizio Lancellotti was awarded an ERC-Conso-
lidator grant «Prosthetic valve bioactive surface
coating to reduce the prevalence of thrombosis: PV-
COAT
»
(European Union’s Horizon 2020 Framework
Programme for Research and Innovation) - see
page 8.
Patrizio Lancellotti acted as co-chair of the Euro-
pean Society Cardiology Guidelines on the mana-
gement of infective endocarditis published in the
European Heart Journal. He has become Asso-
ciate Editor of the European Heart Journal. He is
also member of the Jury of the prestigious Belgian
Galien Price 2015.
Cécile Oury was elected as Board member of the
Belgian Society on Thrombosis and Haemostasis
and of the ANR scientific comittee CES N° 32 –
« Sciences de la Vie IMCE
»
2015. She participated in
the jury of the Scientific Award Foundation AstraZe-
neca – Cardiovascular Diseases 2015.
François Jouret received an Octaaf Dupont award
from the Royal Academy of Medicine of Belgium
for his PhD dissertation. One of his publication was
also rewarded with a prize by the Belgian Society of
Nephrology.
Céline Delierneux, PhD student in Prof Lancellotti
and Dr Oury’s team, received a Young Investigator
Award at the Congress of the International Society
on Thrombosis and Haemostasis that was held in
Toronto, Canada (June 20-25).