Citation
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
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
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
© 2005 Ilze Bot
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