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The effect of glucocorticoids on regulation of the human angiotensinogen gene and blood pressure
Table of Contents
Abstract
Acknowledgements
Table of Contents
List of Figures
List of Schematics
List of Abbreviations
1 Introduction
2 Review of the literature
2.1 Renin-Angiotensin-Aldosterone System (RAAS)
2.2 RAAS in Mammalian Physiology
2.3 Systemic and Tissue Distribution of RAAS
2.4 Genetics of Hypertension
2.5 Role of Genetic Variants of the RAAS in Hypertension
2.6 Role of Glucocorticoids in Hypertension
2.7 The Human Angiotensinogen Gene
2.8 Characteristics of the hAGT Protein
2.9 Regulation of the hAGT Gene
2.10 Association of the hAGT Gene with Hypertension
2.11 Structure of Haplotype -6A and Haplotype -6G of the hAGT Gene
2.12 Structure of the hAGT Promoter
2.13 Glucocorticoid Response Elements in the hAGT Gene
2.14 Comparison of the Putative ‘cis’ Elements in the hAGT Gene with Consensus GRE and HNF-1 Binding Sites
2.15 In vitro Analysis of the Effect of DEX on the Promoter Activity of Haplotype -6A and Haplotype -6G of the hAGT Gene
2.16 Generation of Transgenic Mice with Haplotype -6A and Haplotype -6G of the hAGT Gene
3 Hypothesis and Specific Aims of the Research
4 Materials and Methods
4.1 Animal Care and Use
4.2 Transgenic Mice
4.3 Generation of the Double Transgenic Mice Containing Human AGT and Human Renin
4.4 Dexamethasone Treatment
4.5 Quantitative Real-Time RT-PCR
4.6 Western Blot Analysis
4.7 In-vivo Chromatin Immune-Precipitation Assay
4.8 Measurement of Plasma Angiotensin-II
4.9 Blood Pressure Measurement in Mice
4.10 Statistical Analysis
5 Results
5.1 Dexamethasone Induces Expression of the hAGT Gene in the Liver of Transgenic Mice Containing Hap -6A
5.2 Kidney Shows Increased Expression of the hAGT Gene in Transgenic Mice with Hap -6A in Response to Dexamethasone Treatment
5.3 Treatment with Dexamethasone Causes an Increase in both hAGT as well as Endogenous Mouse AGT in the Adrenals of Transgenic Mice with Haplotype -6A
5.4 ChIP Analysis Shows Binding of GR to the Promoter of the hAGT gene is Increased in the Transgenic Mice with Haplotype -6A on Treatment with Dexamethsone
5.5 DEX Treatment Elicits a Significant Increase in the Plasma hAGT and Ang-II Levels of Transgenic Mice with Haplotype -6A
5.6 Dexamethasone Dependent Modulation of the Systolic Blood Pressure is Affected by the Nucleotide Differences in the ‘cis’ Elements of Hap -6A and Hap -6G of the hAGT Gene
6 Discussion
7 Future Prospects
ReferencesBài viết liên quan
