Cellular senescence impairs the reversibility of pulmonary arterial hypertension

Diederik E. van der Feen; Guido P. L. Bossers; Quint A. J. Hagdorn; Jan-Renier Moonen; Kondababu Kurakula; Robert Szulcek; James Chappell; Francesco Vallania; Michele Donato; Klaas Kok; Jaskaren S. Kohli; Arjen H. Petersen; Tom van Leusden; Marco Demaria; Marie-José T. H. Goumans; Rudolf A. De Boer; Purvesh Khatri; Marlene Rabinovitch; Rolf M. F. Berger; Beatrijs Bartelds

doi:10.1126/scitranslmed.aaw4974

Research ArticlePulmonary Arterial Hypertension

Cellular senescence impairs the reversibility of pulmonary arterial hypertension

View ORCID ProfileDiederik E. van der Feen ¹,*,
Guido P. L. Bossers¹,
View ORCID ProfileQuint A. J. Hagdorn¹,
View ORCID ProfileJan-Renier Moonen²,
Kondababu Kurakula³,
View ORCID ProfileRobert Szulcek⁴,
View ORCID ProfileJames Chappell²,
View ORCID ProfileFrancesco Vallania⁵,⁶,
Michele Donato⁵,⁶,
View ORCID ProfileKlaas Kok⁷,
Jaskaren S. Kohli⁸,
Arjen H. Petersen⁹,
Tom van Leusden¹⁰,
View ORCID ProfileMarco Demaria⁸,
View ORCID ProfileMarie-José T. H. Goumans³,
View ORCID ProfileRudolf A. De Boer¹⁰,
View ORCID ProfilePurvesh Khatri⁵,⁶,
Marlene Rabinovitch ²,
View ORCID ProfileRolf M. F. Berger ¹ and
View ORCID ProfileBeatrijs Bartelds¹,†

¹Center for Congenital Heart Diseases, University Medical Center Groningen, 9713 GZ Groningen, Netherlands.
²Department of Pediatrics, Vera Moulton Wall Center for Pulmonary Vascular Disease and the Cardiovascular Institute, Stanford School of Medicine, Stanford, CA 94305, USA.
³Department of Cell and Chemical Biology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.
⁴Department of Pulmonology, VU University Medical Center, 1081 HV Amsterdam, Netherlands.
⁵Institute for Immunity, Transplantation and Infection, Stanford School of Medicine, Stanford, CA 94305, USA.
⁶Stanford Center of Biomedical Informatics Research, Department of Medicine, Stanford, CA 94305, USA.
⁷Department of Genetics, University Medical Center Groningen, 9713 GZ Groningen, Netherlands.
⁸European Research Institute for the Biology of Ageing, 9700 AD Groningen, Netherlands.
⁹Department of Medical Biology, University Medical Center Groningen, 9713 GZ Groningen, Netherlands.
¹⁰Department of Experimental Cardiology, University Medical Center Groningen, 9713 GZ Groningen, Netherlands.

↵*Corresponding author. Email: d.e.van.der.feen01{at}umcg.nl

↵† Present address: Division of Cardiology, Department of Pediatrics, Erasmus University Medical Center, Rotterdam, the Netherlands.

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Science Translational Medicine 29 Jul 2020:
Vol. 12, Issue 554, eaaw4974
DOI: 10.1126/scitranslmed.aaw4974

Diederik E. van der Feen

1Center for Congenital Heart Diseases, University Medical Center Groningen, 9713 GZ Groningen, Netherlands.

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For correspondence: d.e.van.der.feen01@umcg.nl

Guido P. L. Bossers

1Center for Congenital Heart Diseases, University Medical Center Groningen, 9713 GZ Groningen, Netherlands.

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Quint A. J. Hagdorn

1Center for Congenital Heart Diseases, University Medical Center Groningen, 9713 GZ Groningen, Netherlands.

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ORCID record for Quint A. J. Hagdorn

Jan-Renier Moonen

2Department of Pediatrics, Vera Moulton Wall Center for Pulmonary Vascular Disease and the Cardiovascular Institute, Stanford School of Medicine, Stanford, CA 94305, USA.

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Kondababu Kurakula

3Department of Cell and Chemical Biology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.

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Robert Szulcek

4Department of Pulmonology, VU University Medical Center, 1081 HV Amsterdam, Netherlands.

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James Chappell

2Department of Pediatrics, Vera Moulton Wall Center for Pulmonary Vascular Disease and the Cardiovascular Institute, Stanford School of Medicine, Stanford, CA 94305, USA.

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Francesco Vallania

5Institute for Immunity, Transplantation and Infection, Stanford School of Medicine, Stanford, CA 94305, USA.

6Stanford Center of Biomedical Informatics Research, Department of Medicine, Stanford, CA 94305, USA.

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Michele Donato

5Institute for Immunity, Transplantation and Infection, Stanford School of Medicine, Stanford, CA 94305, USA.

6Stanford Center of Biomedical Informatics Research, Department of Medicine, Stanford, CA 94305, USA.

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Klaas Kok

7Department of Genetics, University Medical Center Groningen, 9713 GZ Groningen, Netherlands.

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Jaskaren S. Kohli

8European Research Institute for the Biology of Ageing, 9700 AD Groningen, Netherlands.

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Arjen H. Petersen

9Department of Medical Biology, University Medical Center Groningen, 9713 GZ Groningen, Netherlands.

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Tom van Leusden

10Department of Experimental Cardiology, University Medical Center Groningen, 9713 GZ Groningen, Netherlands.

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Marco Demaria

8European Research Institute for the Biology of Ageing, 9700 AD Groningen, Netherlands.

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Marie-José T. H. Goumans

3Department of Cell and Chemical Biology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.

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Rudolf A. De Boer

10Department of Experimental Cardiology, University Medical Center Groningen, 9713 GZ Groningen, Netherlands.

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Purvesh Khatri

5Institute for Immunity, Transplantation and Infection, Stanford School of Medicine, Stanford, CA 94305, USA.

6Stanford Center of Biomedical Informatics Research, Department of Medicine, Stanford, CA 94305, USA.

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Marlene Rabinovitch

2Department of Pediatrics, Vera Moulton Wall Center for Pulmonary Vascular Disease and the Cardiovascular Institute, Stanford School of Medicine, Stanford, CA 94305, USA.

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Rolf M. F. Berger

1Center for Congenital Heart Diseases, University Medical Center Groningen, 9713 GZ Groningen, Netherlands.

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Beatrijs Bartelds

1Center for Congenital Heart Diseases, University Medical Center Groningen, 9713 GZ Groningen, Netherlands.

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