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Macrophage regulatory mechanisms in atherosclerosis
The interplay of lipids and inflammation
Neele, A.E.
Publication date
2018
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Citation for published version (APA):
Neele, A. E. (2018). Macrophage regulatory mechanisms in atherosclerosis: The interplay of
lipids and inflammation.
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Macrophage regulatory mechanisms
in atherosclerosis:
the interplay of lipids and inflammation
515552-L-bw-neele 515552-L-bw-neele 515552-L-bw-neele 515552-L-bw-neele Processed on: 1-12-2017 Processed on: 1-12-2017 Processed on: 1-12-2017
Processed on: 1-12-2017 PDF page: 2PDF page: 2PDF page: 2PDF page: 2 Macrophage regulatory mechanisms in atherosclerosis:
the interplay of lipids and inflammation
PhD thesis, University of Amsterdam, The Netherlands Author: Annette Neele
Cover Design: Robin Tuijnenburg & Annette Neele Layout: Annette Neele
Printing: Ipskamp printing ISBN: 978-94-028-0877-3
Copyright 2018 © Annette E. Neele
Financial support by the Dutch Heart Foundation for the publication of this thesis is gratefully acknowledged.
The research described in this thesis was supported by a grant of the Dutch Heart Foundation (CVON 2011B019 Genius).
Further financial support for printing this thesis was kindly provided by the department of Medical Biochemistry (AMC) and Sanofi.
Macrophage regulatory mechanisms
in atherosclerosis:
the interplay of lipids and inflammation
ACADEMISCH PROEFSCHRIFT
ter verkrijging van de graad van doctor aan de Universiteit van Amsterdam op gezag van de Rector Magnificus
prof. dr. ir. K.I.J. Maex
ten overstaan van een door het College voor Promoties ingestelde commissie, in het openbaar te verdedigen in de Agnietenkapel
op vrijdag 19 januari 2018, te 14.00 uur door Annette Elise Neele
515552-L-bw-neele 515552-L-bw-neele 515552-L-bw-neele 515552-L-bw-neele Processed on: 1-12-2017 Processed on: 1-12-2017 Processed on: 1-12-2017
Processed on: 1-12-2017 PDF page: 3PDF page: 3PDF page: 3PDF page: 3 Macrophage regulatory mechanisms in atherosclerosis:
the interplay of lipids and inflammation
PhD thesis, University of Amsterdam, The Netherlands Author: Annette Neele
Cover Design: Robin Tuijnenburg & Annette Neele Layout: Annette Neele
Printing: Ipskamp printing ISBN: 978-94-028-0877-3
Copyright 2018 © Annette E. Neele
Financial support by the Dutch Heart Foundation for the publication of this thesis is gratefully acknowledged.
The research described in this thesis was supported by a grant of the Dutch Heart Foundation (CVON 2011B019 Genius).
Further financial support for printing this thesis was kindly provided by the department of Medical Biochemistry (AMC) and Sanofi.
Macrophage regulatory mechanisms
in atherosclerosis:
the interplay of lipids and inflammation
ACADEMISCH PROEFSCHRIFT
ter verkrijging van de graad van doctor aan de Universiteit van Amsterdam op gezag van de Rector Magnificus
prof. dr. ir. K.I.J. Maex
ten overstaan van een door het College voor Promoties ingestelde commissie, in het openbaar te verdedigen in de Agnietenkapel
op vrijdag 19 januari 2018, te 14.00 uur door Annette Elise Neele
515552-L-bw-neele 515552-L-bw-neele 515552-L-bw-neele 515552-L-bw-neele Processed on: 1-12-2017 Processed on: 1-12-2017 Processed on: 1-12-2017
Processed on: 1-12-2017 PDF page: 4PDF page: 4PDF page: 4PDF page: 4
Promotiecommissie
Promotores: prof. dr. M.P.J. de Winther AMC-Universiteit van Amsterdam
prof. dr. E. Lutgens AMC-Universiteit van Amsterdam
Co-promotores: dr. M.J.J. Gijbels AMC-Universiteit van Amsterdam dr. ir. J. Van den Bossche AMC-Universiteit van Amsterdam Overige leden: prof. dr. C.J.M. de Vries AMC-Universiteit van Amsterdam prof. dr. W.J. de Jonge AMC-Universiteit van Amsterdam
prof. dr. M.J.A.P. Daemen AMC-Universiteit van Amsterdam
prof. dr. N.P. Riksen Radboud Universiteit Nijmegen
prof. dr. J. Kuiper Universiteit Leiden
prof. dr. T.K. van den Berg Vrije Universiteit Amsterdam
515552-L-bw-neele 515552-L-bw-neele 515552-L-bw-neele 515552-L-bw-neele Processed on: 1-12-2017 Processed on: 1-12-2017 Processed on: 1-12-2017
Processed on: 1-12-2017 PDF page: 5PDF page: 5PDF page: 5PDF page: 5
Promotiecommissie
Promotores: prof. dr. M.P.J. de Winther AMC-Universiteit van Amsterdam
prof. dr. E. Lutgens AMC-Universiteit van Amsterdam
Co-promotores: dr. M.J.J. Gijbels AMC-Universiteit van Amsterdam dr. ir. J. Van den Bossche AMC-Universiteit van Amsterdam Overige leden: prof. dr. C.J.M. de Vries AMC-Universiteit van Amsterdam prof. dr. W.J. de Jonge AMC-Universiteit van Amsterdam
prof. dr. M.J.A.P. Daemen AMC-Universiteit van Amsterdam
prof. dr. N.P. Riksen Radboud Universiteit Nijmegen
prof. dr. J. Kuiper Universiteit Leiden
prof. dr. T.K. van den Berg Vrije Universiteit Amsterdam
515552-L-bw-neele 515552-L-bw-neele 515552-L-bw-neele 515552-L-bw-neele Processed on: 1-12-2017 Processed on: 1-12-2017 Processed on: 1-12-2017
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Table of contents
Chapter 1 General introduction 9 Chapter 2 Macrophage polarization: the epigenetic point of view 23 Chapter 3 Epigenetic pathways in macrophages emerge as novel 39
targets in atherosclerosis
Chapter 4 Inhibiting epigenetic enzymes to improve atherogenic 67 macrophage functions
Chapter 5 Macrophage Kdm6b controls the pro-fibrotic transcriptome 89 signature of foam cells
Chapter 6 Myeloid Kdm6b disruption results in advanced atherosclerosis 107
Chapter 7 Myeloid Ezh2 deficiency limits atherosclerosis 125
Chapter 8 Fine tuning of DNA methylation during the differentiation and 143 activation of human macrophages
Chapter 9 PCSK9 monoclonal antibodies reverse the pro-inflammatory 165 profile of monocytes in familial hypercholesterolemia
Chapter 10 Discussion and future perspectives 199
Appendixes Summary 213
Nederlandse samenvatting 219
PhD portfolio 225
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Table of contents
Chapter 1 General introduction 9 Chapter 2 Macrophage polarization: the epigenetic point of view 23 Chapter 3 Epigenetic pathways in macrophages emerge as novel 39
targets in atherosclerosis
Chapter 4 Inhibiting epigenetic enzymes to improve atherogenic 67 macrophage functions
Chapter 5 Macrophage Kdm6b controls the pro-fibrotic transcriptome 89 signature of foam cells
Chapter 6 Myeloid Kdm6b disruption results in advanced atherosclerosis 107
Chapter 7 Myeloid Ezh2 deficiency limits atherosclerosis 125
Chapter 8 Fine tuning of DNA methylation during the differentiation and 143 activation of human macrophages
Chapter 9 PCSK9 monoclonal antibodies reverse the pro-inflammatory 165 profile of monocytes in familial hypercholesterolemia
Chapter 10 Discussion and future perspectives 199
Appendixes Summary 213
Nederlandse samenvatting 219
PhD portfolio 225
