Platelet Transcriptome Profiling in HIV and ATP-Binding Cassette Subfamily C Member 4 (ABCC4) as a Mediator of Platelet Activity

Emanuela Marcantoni, PhD; Nicole Allen, BS; Matthew R. Cambria, BA; Rebecca Dann, BS; Michael Cammer, BS; Tenzin Lhakhang, BS; Meagan P. O’Brien, MD; Benjamin Kim, BS; Tilla Worgall, MD, PhD; Adriana Heguy, PhD; Aristotelis Tsirigos, PhD; Jeffrey S. Berger, MD, MS

doi:10.1016/j.jacbts.2017.10.005

JACC: Basic to Translational Science (Feb 2018)

Platelet Transcriptome Profiling in HIV and ATP-Binding Cassette Subfamily C Member 4 (ABCC4) as a Mediator of Platelet Activity

Emanuela Marcantoni, PhD,
Nicole Allen, BS,
Matthew R. Cambria, BA,
Rebecca Dann, BS,
Michael Cammer, BS,
Tenzin Lhakhang, BS,
Meagan P. O’Brien, MD,
Benjamin Kim, BS,
Tilla Worgall, MD, PhD,
Adriana Heguy, PhD,
Aristotelis Tsirigos, PhD,
Jeffrey S. Berger, MD, MS

Affiliations

Emanuela Marcantoni, PhD: Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, New York
Nicole Allen, BS: Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, New York
Matthew R. Cambria, BA: Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, New York
Rebecca Dann, BS: Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, New York
Michael Cammer, BS: DART Microscopy Laboratory, NYU Langone Medical Center, New York, New York
Tenzin Lhakhang, BS: Applied Bioinformatics Laboratories, New York University School of Medicine, New York, New York
Meagan P. O’Brien, MD: Divisions of Infectious Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
Benjamin Kim, BS: Department of Pathology and Cell Biology, Columbia University, New York, New York
Tilla Worgall, MD, PhD: Department of Pathology and Cell Biology, Columbia University, New York, New York
Adriana Heguy, PhD: Department of Pathology, New York University School of Medicine, New York, New York
Aristotelis Tsirigos, PhD: Applied Bioinformatics Laboratories, New York University School of Medicine, New York, New York
Jeffrey S. Berger, MD, MS: Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, New York

DOI: https://doi.org/10.1016/j.jacbts.2017.10.005
Journal volume & issue: Vol. 3, no. 1
pp. 9 – 22

Abstract

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An unbiased platelet transcriptome profile identified ATP binding cassette subfamily C member 4 (ABCC4) as a novel mediator of platelet activity in virologically suppressed human immunodeficiency virus (HIV)-infected subjects on antiretroviral therapy. Using ex vivo and in vitro cellular and molecular assays we demonstrated that ABCC4 regulated platelet activation by altering granule release and cyclic nucleotide homeostasis through a cAMP-protein kinase A (PKA)–mediated mechanism. Platelet ABCC4 inhibition attenuated platelet activation and effector cell function by reducing the release of inflammatory mediators, such as sphingosine-1-phosphate. ABCC4 inhibition may represent a novel antithrombotic strategy in HIV-infected subjects on antiretroviral therapy.

Published in JACC: Basic to Translational Science

ISSN: 2452-302X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system
Website: https://www.journals.elsevier.com/jacc-basic-to-translational-science/

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Abstract

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