The matricellular protein TSP1 promotes human and mouse endothelial cell senescence through CD47 and Nox1

Daniel N. Meijles; Sanghamitra Sahoo; Imad Al Ghouleh; Jefferson H. Amaral; Raquel Bienes-Martinez; Heather E. Knupp; Shireen Attaran; John C. Sembrat; Seyed M. Nouraie; Mauricio M. Rojas; Enrico M. Novelli; Mark T. Gladwin; Jeffrey S. Isenberg; Eugenia Cifuentes-Pagano; Patrick J. Pagano

doi:10.1126/scisignal.aaj1784

Research ArticleAging

The matricellular protein TSP1 promotes human and mouse endothelial cell senescence through CD47 and Nox1

Daniel N. Meijles¹,²,*,
Sanghamitra Sahoo¹,²,
Imad Al Ghouleh¹,²,³,
Jefferson H. Amaral¹,²,
Raquel Bienes-Martinez¹,
Heather E. Knupp¹,
Shireen Attaran²,
John C. Sembrat¹,²,
Seyed M. Nouraie⁴,
Mauricio M. Rojas¹,⁴,
Enrico M. Novelli¹,
Mark T. Gladwin¹,⁴,
Jeffrey S. Isenberg¹,²,⁴,
Eugenia Cifuentes-Pagano¹,², and
Patrick J. Pagano¹,²,†

¹Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.
²Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
³Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
⁴Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.

↵†Corresponding author. Email: pagano{at}pitt.edu

↵* Present address: Molecular and Clinical Sciences Research Institute, St. George’s University of London, London SW17 0RE, UK.

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Science Signaling 17 Oct 2017:
Vol. 10, Issue 501, eaaj1784
DOI: 10.1126/scisignal.aaj1784

Daniel N. Meijles

Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.

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ORCID record for Daniel N. Meijles

Sanghamitra Sahoo

Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.

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Imad Al Ghouleh

Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.

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Jefferson H. Amaral

Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.

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Raquel Bienes-Martinez

Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.

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Heather E. Knupp

Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.

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Shireen Attaran

Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.

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John C. Sembrat

Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.

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Seyed M. Nouraie

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.

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ORCID record for Seyed M. Nouraie

Mauricio M. Rojas

Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.

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Enrico M. Novelli

Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.

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Mark T. Gladwin

Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.

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Jeffrey S. Isenberg

Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.

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Eugenia Cifuentes-Pagano

Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.

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Patrick J. Pagano

Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.

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For correspondence: pagano@pitt.edu

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The matricellular protein TSP1 promotes human and mouse endothelial cell senescence through CD47 and Nox1

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