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Table of contents
Introduction
1. Cardiovascular diseases (CVDs)- the main cause of death in europe
1.1. Atherosclerosis – a chronic inflammatory disease
1.2. Lipoproteins- role of oxidized LDL in atherosclerosis
2. Macrophage polarization- a response to the microenvironment
3. Oxidative Stress – the underlying cause of many disease
4. The thioredoxin system
4.1. The thioredoxin-1 gene
4.2. Structure of thioredoxin-1
4.3. Truncated thioredoxin (Trx80)
4.4. The thioredoxin reductases
4.5. Thioredoxin interacting protein (TXNIP)
4.6. Regulation and post-translational modifications of thioredoxin-1
4.7. General functions of Trx1
4.8. Role of Trx1 in apoptosis
4.9. Trx regulates glucocorticoid and estrogen receptors
4.10. The Trx system and Aging
4.11. The Trx system in cardiovascular diseases
5.Context of the project
Results and discussion
6. Thioredoxin-1 induces M2 polarization
6.1. Study presentation
6.2. Article I
7. Truncated thioredoxin induces M1 polarization
7.1. Study presentation
7.2. Article II
8. Possible signaling pathway involved in macrophage polarization
8.1. Study presentation
8.2. Regulation of cell signaling by Trx1
8.2.1. Extracellular Trx1
8.2.2. Cytoplasmic Trx1
8.2.2.1. Mitogen-activated protein kinases
8.2.2.2. Calcium signaling
8.2.3. Nuclear Trx1
8.3. The mTOR signaling pathway
8.4. Materials and methods
8.4.1. Extracellular Trx1 Isolation and treatment of mouse peritoneal macrophages
8.4.2. Western Blot Analysis
8.5. Results
8.5.1. Both Trx1 and Trx80 activate Akt
8.5.2. Trx80, but not Trx1, activates mTOR
8.5.3. Inhibition of mTOR downregulated the expression of inflammatory cytokines
8.5.4. Trx80 activates mTOR in dose-dependent manner
8.5.5. mTOR inhibition orientes resting macrophages toward M2 phenotypes
8.6. Discussion
General Discussion
Conclusions
References
