- Author
-
K.R. Pertiwi
- Title
- Novel aspects of innate immunity in human atherosclerosis and thrombosis
- Supervisors
-
A.C. van der Wal
- Co-supervisors
-
O.J. de Boer
- Award date
- 23 June 2020
- Number of pages
- 194
- ISBN
- 9789463808279
- Document type
- PhD thesis
- Faculty
- Faculty of Medicine (AMC-UvA)
- Abstract
-
Atherosclerotic plaque disruption followed by thrombus formation, can lead to fatal diseases, such as myocardial infarction and stroke, when the thrombus occludes the vessel-wall. Thrombus formation does not always cause sudden occlusion but is often started days even weeks before the acute event. This thesis investigated whether inflammatory responses are involved in the process from thrombus outgrowth to occlusive lesion. The main findings are that neutrophils and neutrophil extracellular traps (NETs), hardly occurred in intact-, but were found large quantities in thrombosed plaques. Not only granulocytes but also mast cells, eosinophils and macrophages were found to release ETs, albeit to a lesser extent. The generation of ETs, marking a distinct form of cell death (etosis) increased significantly with the age of thrombus, and etosis even appeared to be the major form of cell death in the organizing thrombus. Subsets of innate lymphoid cells, a relatively new family of immune cells and not previously described in human plaques, could be identified in all developing stages of atherogenesis. Moreover, we performed a clinical-pathological follow-up study of patients who had thrombosuction in the coronaries or in the cerebral vessels. The composition and the age of the thrombus were positively correlated with the risk of mortality in patients with myocardial infarction and stroke. We postulate that thrombus age and ETs (mainly released by neutrophils) and other innate inflammatory cells can act as biomarkers for thrombus (in)stability. Furthermore, ETs and ILCs could potentially act as targets for treatment of patients with acute atherothrombotic disease.
- Persistent Identifier
- https://hdl.handle.net/11245.1/b466acd1-8607-41db-9275-c3eab5f88582
- Downloads
-
Thesis (complete)
Front matter
Chapter 1: General introduction
Chapter 2: Neutrophil extracellular traps participate in all different types of thrombotic and haemorrhagic complications of coronary atherosclerosis
Chapter 3: Extracellular traps derived from macrophages, eosinophils, mast cells and neutrophils occur are generated in a time-dependent manner during atherothrombosis
Chapter 4: Etosis, rather than apoptosis or cell proliferation, typifies thrombus progression – An immunohistochemical study of coronary aspirates
Chapter 5: Immunophenotypic analysis of the chronological events of tissue repair in aortic medial dissections
Chapter 6: Novel players in human atherosclerotic plaque inflammation: Innate lymphoid cells are present in all developmental stages of plaque formation
Chapter 7: Histopathological thrombus study in large vessel occlusion related stroke and ST-segment elevation myocardial infarction: Similarities, differences, and prognostic implications
Chapter 8: Summary and discussion
Appendix; List of contributing authors; PhD portfolio; List of publications; Acknowledgement
Propositions
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