Adipose tissue–derived WNT5A regulates vascular redox signaling in obesity via USP17/RAC1-mediated activation of NADPH oxidases

Ioannis Akoumianakis; Fabio Sanna; Marios Margaritis; Ileana Badi; Nadia Akawi; Laura Herdman; Patricia Coutinho; Harry Fagan; Alexios S. Antonopoulos; Evangelos K. Oikonomou; Sheena Thomas; Amy P. Chiu; Surawee Chuaiphichai; Christos P. Kotanidis; Constantinos Christodoulides; Mario Petrou; George Krasopoulos; Rana Sayeed; Lei Lv; Ashley Hale; Meisam Naeimi Kararoudi; Eileen McNeill; Gillian Douglas; Sarah George; Dimitris Tousoulis; Keith M. Channon; Charalambos Antoniades

doi:10.1126/scitranslmed.aav5055

Research ArticleCARDIOMETABOLIC DISEASE

Adipose tissue–derived WNT5A regulates vascular redox signaling in obesity via USP17/RAC1-mediated activation of NADPH oxidases

Ioannis Akoumianakis¹,*,
Fabio Sanna¹,*,
Marios Margaritis¹,
Ileana Badi¹,
Nadia Akawi¹,
Laura Herdman¹,
Patricia Coutinho¹,
Harry Fagan¹,
Alexios S. Antonopoulos¹,
Evangelos K. Oikonomou¹,
Sheena Thomas¹,
Amy P. Chiu¹,
Surawee Chuaiphichai¹,
Christos P. Kotanidis¹,
Constantinos Christodoulides ²,
Mario Petrou³,
George Krasopoulos³,
Rana Sayeed³,
Lei Lv¹,
Ashley Hale¹,
Meisam Naeimi Kararoudi¹,
Eileen McNeill¹,
Gillian Douglas¹,
Sarah George⁴,
Dimitris Tousoulis⁵,
Keith M. Channon ¹ and
Charalambos Antoniades ¹,†

¹Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.
²Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, OX3 7LE, UK.
³Department of Cardiothoracic Surgery, Oxford University Hospitals NHS Trust, Oxford, OX3 9DU, UK.
⁴Bristol Medical School, University of Bristol, Research Floor Level 7, Bristol Royal Infirmary, Bristol BS2 8HW, UK.
⁵Cardiology Department, Athens University Medical School, Athens 115 27, Greece.

↵†Corresponding author. Email: antoniad{at}well.ox.ac.uk

↵* These authors contributed equally to this work.

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Science Translational Medicine 18 Sep 2019:
Vol. 11, Issue 510, eaav5055
DOI: 10.1126/scitranslmed.aav5055

Ioannis Akoumianakis

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.

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Fabio Sanna

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.

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Marios Margaritis

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.

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Ileana Badi

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.

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Nadia Akawi

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.

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Laura Herdman

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.

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Patricia Coutinho

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.

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Harry Fagan

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.

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Alexios S. Antonopoulos

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.

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Evangelos K. Oikonomou

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.

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Sheena Thomas

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.

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Amy P. Chiu

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.

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Surawee Chuaiphichai

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.

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Christos P. Kotanidis

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.

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Constantinos Christodoulides

Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, OX3 7LE, UK.

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Mario Petrou

Department of Cardiothoracic Surgery, Oxford University Hospitals NHS Trust, Oxford, OX3 9DU, UK.

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George Krasopoulos

Department of Cardiothoracic Surgery, Oxford University Hospitals NHS Trust, Oxford, OX3 9DU, UK.

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Rana Sayeed

Department of Cardiothoracic Surgery, Oxford University Hospitals NHS Trust, Oxford, OX3 9DU, UK.

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Lei Lv

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.

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Ashley Hale

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.

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Meisam Naeimi Kararoudi

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.

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Eileen McNeill

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.

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Gillian Douglas

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.

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Sarah George

Bristol Medical School, University of Bristol, Research Floor Level 7, Bristol Royal Infirmary, Bristol BS2 8HW, UK.

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Dimitris Tousoulis

Cardiology Department, Athens University Medical School, Athens 115 27, Greece.

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Keith M. Channon

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.

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Charalambos Antoniades

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.

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For correspondence: antoniad@well.ox.ac.uk

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Adipose-secreted WNT5A triggers vascular disease in obesity, activating vascular smooth muscle cell migration by an NADPH oxidase–dependent mechanism.

Adipose tissue–derived WNT5A regulates vascular redox signaling in obesity via USP17/RAC1-mediated activation of NADPH oxidases

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