(Downloads - 0)
For more info about our services contact : help@bestpfe.com
Table of contents
CHAPTER 1 – INTRODUCTION
I. Pharmacogenomics of Anti-inflammatory Effects of Thienopyridines
1. Pharmaco-genetics, -genomics and personalized medicine
2. P2Y12 receptor antagonists including thienopyridines
2.1. Clopidogrel
2.1.1. Anti-inflammatory effects of clopidogrel
2.2. Prasugrel
2.2.1. Anti-inflammatory effects of prasugrel
3. References
II. Influences of Inter-tissue, Inter-individual and Intra-individual Variability in the Expression of Human Cytochrome P450 Epoxygenases on Epoxyeicosatrienoic Acids-m
1. Introduction
2. Cytochrome P450, Epoxyeicosatrienoic acids; General considerations
2.1. CYP enzyme; structure
2.2. CYP enzyme; catalytic activity
2.3. Human CYP epoxygenases; EET formation
2.4. Physiological roles of EETs in vascular biology
2.5. Nuclear receptor-mediated transcriptional regulation of CYP epoxygenase genes
2.6. MicroRNA-mediated transcriptional and post-transcriptional regulation of CYP genes
2.7. Epigenetic-mediated transcriptional and post-transcriptional regulation of CYP genes
2.8. NR-epigenetic-miRNA network-mediated regulation of CYP epoxygenases
2.9. Genes counter-interaction
3. Inter- and intra-individual variability in CYP expression
3.1. Age
3.2. Gender
3.3. Molecular genetics
3.3.1. Variation in POR expression
3.3.2. Polymorphisms of genes encoding NRs and NR binding sites
3.3.3. MicroRNAs
3.3.4. Epigenetic factors
3.3.5. CYP gene polymorphism
3.3.5.1. Copy number variation
3.4. Xenobiotics
3.5. Environmental factors
3.6. Sex steroid-dependent states
3.7. Immunological response – local/systemic disorders
3.8. Nervous system and stress mediated CYP regulation
3.9. Radiation
4. Inter-tissue variability in CYP epoxygenase expression
4.1. CYP expression in liver
4.2. CYP expression in gastrointestinal tract
4.3. CYP expression in respiratory tract
4.4. CYP expression in genitourinary system
4.5. CYP expression in central nervous system
4.6. CYP expression in cardiocirculatory system
5. Inter-tissue, inter- and intra-individual variability in CYP epoxygenases; clinical implication
6. Summary
7. References
III. Influence of Inflammation on Cardiovascular Protective Effects of Cytochrome P450 Epoxygenase-Derived Epoxyeicosatrienoic Acids
1. Vascular arachidonic acid metabolism
2. EETs synthesis and metabolism; overview
3. CYP epoxygenases expression and EET resources in cardiovascular system
4. Physiological roles of EETs in cardiovascular system
4.1. EETs and myocardial function
4.2. EETs and vascular function
4.2.1. EETs and vasodilation
4.2.2. EETs and vascular homeostasis
4.2.2.1. EETs and regulation of angiogenesis, fibrinolysis, apoptosis and SMCs migration
4.2.2.2. CYP epoxygenase-derived EETs and inflammation
4.2.2.2.1. CYP epoxygenase-derived EETs and inhibition of EC activation
4.2.2.2.1.1. NF-κB and inflammation
4.2.2.2.1.1.1. NF-κB; structure and activation pathways
4.2.2.2.1.1.2. CYP epoxygenase-derived EETs as NF-κB inhibitors
4.2.2.2.1.2. CYP epoxygenase-derived EETs and activation of PPAR and EGF receptor
4.2.2.2.1.3. CYP epoxygenase-derived EETs and inhibition of LOX-5 and COX-2
4.2.2.2.1.4. CYP epoxygenase-derived EETs and increase HO-1 expression
4.2.2.2.1.5. CYP epoxygenase-derived EETs and increase eNOS expression .
4.2.2.2.2. CYP epoxygenase-derived EETs and platelet inhibition
4.2.2.3. Effect of inflammation on CYP epoxygenase expression
5. Inflammation, CYP epoxygenase expression and EET generation; a vicious cycle?
6. Conclusion and perspective
7. References
IV. Point-of-care pharmacogenetic testing
CHAPTER 2 – HYPOTHESES AND OBJECTIVES
CHAPTER 3 – POPULATIONS AND METHODS
1. SC
1.1. Sample reference population
1.2. Genotyping
1.3. Hp measurement
2. Populations on Thienopyridines
2.1. Paris Study
2.1.1. Measurement of inflammatory markers
2.1.2. Genotyping
2.2. Marseille Study
2.2.1. Biochemical profile
2.2.2. Genotyping
2.2.3. Platelet function measurement
2.3. Liverpool Study
CHAPTER 4 – RESULTS
References
Association between CRP Levels and High on-treatment Platelet Reactivity in Post-PCI on-Thienopyridine Patients
CHAPTER 5 – GENERAL DISCUSSION AND PERSPECTIVES
I. Thesis main findings
II. Inflammation, CVD and post-PCI ISR
1. Platelets: key players in vascular inflammation
1.1. Platelet interaction with ECs
1.1. Platelet interaction with leukocytes
1.2. Activated platelets and CRP, Hp and orosomucoid acid
2. Inflammation and post-PCI complications
2.1. ISR after DES vs. BMS
III. CYP and Metabolism of EETs and Thienopyridines
IV. Thienopyridine Resistance, Non-responsiveness and High On-treatment Platelet Reactivity
1. Resistance, hypo-, non-responsiveness to thienopyridines
2. High on-treatment platelet reactivity
3. Resistance vs. high on-treatment platelet reactivity
V. Smoker’s paradox
VI. Necessity of experimental studies?
VII. Perspectives
2.1. EET measurement:
VIII. References
CHAPTER 6 – Résumé de Thèse En Français
A. Introduction
B. Hypothèses et objectifs
C. Populations
D. Résultats
E. Discussions
F. Perspectives
