E.N. ter Horst
- Clinical and experimental observations on the inflammatory response following a myocardial infarction
A.M. van der Laan
- Award date
- 19 October 2018
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
During a myocardial infarction (MI), ischaemia damages the myocardial tissue distal to the occluded coronary artery which then culminates in apoptotic or necrotic cell death of the affected cardiomyocytes. This immediately triggers the immune system to eliminate and replace the damaged cells with scar tissue. Accumulating evidence emphasize that an exaggerated post-MI immune response directly negatively affects the prognosis after MI.
The studies described in the thesis of Ellis ter Horst aimed to clarify the important aspects of both the innate and the adaptive immune system following MI in clinical and in experimental settings. This elucidated several promising aspects by which monocytes, macrophages, CD4+ T cells and also oxidative stress challenged cardiomyocytes could be modulated to beneficially improve post-MI cardiac healing and to diminish putative cardiac failure. This thesis also revealed that accurate intervention is highly dependent on timely modulation of the immune cells. The intervention should namely 1.) not interfere with the immune response required for proper healing but also 2.) should prevent detrimental aspects of the immune response that deteriorate post-MI cardiac healing. Future studies performed in MI patients should reveal which strategies, that ameliorated cardiac healing in experimental studies, are useful to translate into clinical settings. Hopefully, the studies described in the current thesis will contribute to the development new therapeutic targets which eventually diminish the development of cardiac failure in patients after MI.
- Please note that the acknowledgements section is not included in the thesis downloads.
Thesis (Embargo up to and including 19 October 2020)
Chapter 4: NOX4 is expressed differentially in human monocyte subsets (Embargo up to and including 19 October 2020)
Chapter 5: Elevated monocyte specific type I interferon signalling correlates positively with cardiac healing in myocardial infarct patients but interferon-alpha application deteriorates myocardial healing in rats (Embargo up to and including 19 October 2020)
Chapter 6: Myocardial infarction favors the development of cardioprotective antigen-specific T helper cell responses (Embargo up to and including 19 October 2020)
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