Modulation of the immune system for treatment of atherosclerosis

Leiden Repository

Modulation of the immune system for treatment of atherosclerosis

Type: Doctoral Thesis
Title: Modulation of the immune system for treatment of atherosclerosis
Author: Schaftenaar, F.H.
Issue Date: 2019-12-05
Keywords: Cardiovascular Disease
Atherosclerosis
Immunomodulation
CD8 T-cells
Regulatory T-cells
B-cells
IL-2 complex
Immunoproteasome
Oral Tolerance
p210
Abstract: Cardiovascular 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.
Promotor: Supervisor: Kuiper J. Co-Supervisor: Puijvelde G.H.M. van
Faculty: Faculty of Science
University: Leiden University
Uri: urn:isbn:9789402818017
Handle: http://hdl.handle.net/1887/81382
 

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