Persistent URL of this record https://hdl.handle.net/1887/81382
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Modulation of the immune system for treatment of atherosclerosis
As cholesterol is not soluble in water, cholesterol is transported in the bloodstream in particles called lipoproteins. The...Show moreCardiovascular diseases are the primary cause of death in the world with atherosclerosis as primary underlying cause. Atherosclerosis is characterized by cholesterol accumulation in the vessel wall and inflammation of the vessel wall of medium to large size arteries. Both cholesterol accumulation and inflammation are pathogenic in the context of atherosclerosis. Current treatment regimens are tailored to reduce cholesterol levels in the blood. However, even a successful lowering of cholesterol is in many patients not sufficient to prevent a major cardiovascular event due to unresolved inflammation. Therefore, the immune system provides an interesting therapeutic target for the treatment of atherosclerosis. In this thesis we have explored the effect on atherosclerosis of several immunomodulatory strategies in pre-clinical models.
As cholesterol is not soluble in water, cholesterol is transported in the bloodstream in particles called lipoproteins. The low-density lipoprotein (LDL) carries the highest concentration of cholesterol and accumulates in the vessel wall where a pathogenic specific immune response against LDL is instigated. In this thesis we have used several strategies to modulate the specific immune response against LDL, inducing LDL-specific regulatory T cells, antibodies, and cytotoxic T cells. Through immunoproteasomal inhibition we assessed the effect of general immune inhibition on atherosclerosis.Show less
- All authors
- Schaftenaar, F.H.
- Supervisor
- Kuiper, J.
- Co-supervisor
- Puijvelde, G.H.M. van
- Committee
- Irth, H.; Bouwstra, J.A.; Jager, S.C.A. de; Winther, M.P.J. de; Nilsson, J.
- Qualification
- Doctor (dr.)
- Awarding Institution
- Leiden Academic Centre for Drug Research (LACDR), Faculty of Science, Leiden University
- Date
- 2019-12-05
- ISBN (print)
- 9789402818017
Funding
- Sponsorship
- This research received support from the European Union’s Seventh Framework Programme (FP7/ 2007-2013) under grant agreement VIA no. 603131, which was also supported by financial contribution from Academic and SME/industrial partners. We further acknowledge the support from the Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation, Dutch Federation of University Medical Centres, the Netherlands Organisation for Health Research and Development, and the Royal Netherlands Academy of Sciences for funding the the GENIUS II project (CVON2017-2020). Financial support by the Dutch Heart Foundation for the publication of this thesis is gratefully acknowledged. The realization of this thesis was also financially supported by the Leiden University.