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Modulation of Atherothrombotic Factors: Novel Strategies for Plaque Stabilization

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Bot, I. (2005, September 22). Modulation of Atherothrombotic Factors: Novel Strategies for

Plaque Stabilization. Retrieved from https://hdl.handle.net/1887/3296

Version:

Corrected Publisher’s Version

License:

Licence agreement concerning inclusion of doctoral thesis in the

Institutional Repository of the University of Leiden

Downloaded from:

https://hdl.handle.net/1887/3296

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Modulation of Atherothrombotic Factors:

Novel Strategies for Plaque Stabilization

PROEFSCHRIFT ter verkrijging van

de graad van Doctor aan de Universiteit Leiden, op gezag van de Rector Magnificus Dr. D.D. Breim er,

hoogleraar in de faculteit der W iskunde en Natuurwetenschappen en die der Geneeskunde,

volgens besluit van het College voor Prom oties te verdedigen op donderdag 22 septem ber 2005

klokke 15.15 uur

door

Ilze Bot geboren te Dordrecht

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The studies presented in this thesis were supported by grant 016.026.019 from the Netherlands Organization for Scientific Research (ZonMW) and were performed at the Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands. Financial support by the Netherlands Heart Foundation for the publication of this thesis is gratefully acknowledged.

The printing of this thesis was financially supported by: - Leids Universiteits Fonds

- LACDR

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© 2005 Ilze Bot

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Contents

Page

Chapter 1 General introduction 9

Section 1: Matrix and Cell Homeostasis in Atherosclerotic Plaques 43

Chapter 2 Serine Protease Inhibitor Serp-1 Strongly Impairs 45

Atherosclerotic Lesion Formation and Induces a

Stable Plaque Phenotype in ApoE-/- Mice

Chapter 3 Viral Cross-Class Serpin Inhibits Apoptosis, 61

Inflammation and Atherosclerosis

Chapter 4 Atherosclerotic Lesion Progression Changes 77

Lysophosphatidic Acid Homeostasis to Favor Its Accumulation

Section 2: Inflammation and Plaque Stabilization 89

Chapter 5 Low Dose FK506 Blocks Collar-Induced 91

Atherosclerotic Plaque Development and Stabilizes

Plaques in ApoE-/-Mice

Chapter 6 Adventitial Mast Cell Activation Causes 109

Atherosclerotic Plaque Destabilization in ApoE-/- mice

Chapter 7 Lentiviral ShRNA Silencing of Murine Bone Marrow 127

Cell CCR2 Leads to Persistent Knockdown of CCR2 Function in vivo

Chapter 8 General Discussion and Perspectives 145

Summary 163

Nederlandse Samenvatting 167

Abbreviations 172

Publications 174

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