by Lo Man-har. / Thesis (M.Sc.)--Chinese University of Hong Kong, 1994. / Includes bibliographical references (leaves 56-63). / LIST OF FIGURES --- p.5 / LIST OF TABLES --- p.6 / ACKNOWLEDGEMENTS --- p.8 / SUMMARY --- p.9 / Chapter 1. --- INTRODUCTION --- p.11 / Chapter 1.1 --- Lipid metabolism --- p.11 / Chapter 1.1.1 --- Chylomicron --- p.12 / Chapter 1.1.2 --- Very low density lipoprotein --- p.12 / Chapter 1.1.3 --- Low density lipoprotein --- p.13 / Chapter 1.1.4 --- High density lipoprotein --- p.14 / Chapter 1.2 --- Apolipoprotein B --- p.14 / Chapter 1.3 --- Apolipoprotein B gene --- p.15 / Chapter 1.4 --- Genetic variations in human apo B gene and their associations with abnormal lipid metabolism --- p.16 / Chapter 1.4.1 --- Abetalipoproteinemia --- p.16 / Chapter 1.4.2 --- Hypobetalipoproteinemia --- p.17 / Chapter 1.4.3 --- Familial hypercholesterolemia (FH) --- p.17 / Chapter 1.5 --- Polymorphisms of apo B gene --- p.17 / Chapter 1.6 --- Methods for detection of polymorphisms --- p.19 / Chapter 2. --- OBJECTIVES --- p.20 / Chapter 3. --- MATERIALS AND METHODS --- p.21 / Chapter 3.1 --- Materials and equipments --- p.21 / Chapter 3.1.1 --- Enzymes --- p.21 / Chapter 3.1.2 --- DNA markers --- p.21 / Chapter 3.1.3 --- General reagents --- p.21 / Chapter 3.1.4 --- Equipments --- p.22 / Chapter 3.2 --- Buffers --- p.22 / Chapter 3.3 --- Agarose gel electrophoresis --- p.22 / Chapter 3.4 --- Study subjects --- p.23 / Chapter 3.4.1 --- Cord blood samples --- p.23 / Chapter 3.4.2 --- Geriatric subjects --- p.23 / Chapter - --- Cases --- p.23 / Chapter - --- Controls --- p.24 / Chapter 3.5 --- Clinical Data --- p.24 / Chapter 3.6 --- Blood collection --- p.24 / Chapter 3.7 --- Biochemical analysis --- p.25 / Chapter 3.8 --- DNA extractions --- p.25 / Chapter 3.9 --- Polymerase chain reaction (PCR) --- p.26 / Chapter - --- Oligonucleotide primers --- p.26 / Chapter - --- Signal peptide insertion/deletion polymorphism --- p.26 / Chapter - --- Xba I polymorphism --- p.27 / Chapter - --- Eco RI polymorphism --- p.28 / Chapter 3.10 --- Data analysis --- p.29 / Chapter 4. --- RESULTS --- p.30 / Chapter 4.1 --- Optimization of PCR --- p.30 / Chapter 4.2 --- Clinical features of the case and control subjects --- p.30 / Chapter 4.3 --- Genotyping --- p.31 / Chapter 5. --- DISCUSSION --- p.33 / Chapter 5.1 --- Optimization of PCR protocols --- p.33 / Chapter 5.2 --- Clinical data --- p.34 / Chapter 5.3 --- Allelic frequencies of the three polymorphisms of apo B gene --- p.35 / Chapter 5.4 --- Association of polymorphisms of apo B gene with the case group --- p.36 / Chapter 5.5 --- Association of polymorphisms of apo B gene with hyperlipidaemia --- p.36 / Chapter - --- Signal peptide insertion/deletion polymorphism --- p.36 / Chapter - --- Xba I polymorphism --- p.38 / Chapter - --- Eco RI polymorphism --- p.38 / Chapter 5.6 --- Conclusion --- p.39 / APPENDIX I --- p.53 / APPENDIX II --- p.54 / Chapter 6. --- REFERENCES --- p.56

Urotensin-II (U-II) and its receptor UT are upregulated in the pathological setting of various cardiovascular diseases including atherosclerosis. However, their exact role in atherosclerosis remains to be determined. In the present study, we hypothesized that selective overexpression of UT in an SMC-specific fashion would increase atherosclerotic lesion formation in a hypercholesterolemic mouse model. The objectives were to demonstrate the role of UT in this mouse model of atherosclerosis, and to elucidate some of the mechanism involved in the process. We used four strains of mice; wildtype (WT), UT+ (a transgenic strain expressing human UT driven by the alpha-SM22 promoter), ApoE knockout (ko), and UT+/ApoE ko. All animals were fed a high-fat diet for 12 weeks. Western blot analysis revealed a significant increase in UT expression in UT+ and ApoE ko mice (P<0.05). Serum cholesterol and triglyceride levels were significantly increased in ApoE ko and in UT+/ApoE ko but not in UT + mice when compared to wild type mice (P<0.0001). Analysis of aortas showed a significant increase in atherosclerotic lesion in the UT +, ApoE ko and UT+/ApoE ko compared to WT mice (P<0.05). Oral administration of the UT receptor antagonist SB-657510A for 10 weeks in a group of ApoE ko mice fed a high fat diet resulted in a significant reduction of lesion (P<0.001). Immunohistochemistry revealed the presence of strong expression of UT and U-II proteins in the atheroma of UT+, ApoE ko and UT+/ApoE ko mice, particularly in foam cells. SB-657510A also significantly reduced ACAT-1 protein expression in the atherosclerotic lesion of ApoE ko mice (P<0.05). The present findings suggest that the use of UT receptor antagonists may reduce lesion formation through reduced foam cell formation and lipid uptake, demonstrating an important role for UT in the pathogenesis of atherosclerosis.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

No description available.

by Ma Suk Ling. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 106-129). / Abstracts in English and Chinese. / Abstract --- p.i / 摘要 --- p.iii / Acknowledgements --- p.v / Publications --- p.vi / Abbreviations --- p.vii / Chapter Chapter 1 --- General Introduction --- p.1 / Chapter 1.1 --- Epidemiology of AD --- p.2 / Chapter 1.2 --- Clinical and pathological features of AD --- p.3 / Chapter 1.2.1 --- Clinical features of AD --- p.3 / Chapter 1.2.2. --- Pathological features of AD --- p.3 / Chapter 1.3 --- Diagnosis of AD --- p.4 / Chapter 1.4 --- Classification of AD --- p.5 / Chapter 1.5 --- Causes of AD --- p.5 / Chapter 1.6 --- Risk factors --- p.5 / Chapter 1.6.1 --- Age --- p.5 / Chapter 1.6.2 --- Family history --- p.6 / Chapter 1.6.3 --- Genetics --- p.6 / Chapter 1.6.3.1 --- Autosomal dominant mutations --- p.6 / Chapter 1.6.3.2 --- Genotypes of Apolipoprotein E --- p.6 / Chapter 1.6.4 --- Environmental factors --- p.7 / Chapter Chapter 2 --- Pathology in Alzheimer's disease --- p.8 / Chapter 2.1 --- Overview of Alzheimer's disease pathology --- p.8 / Chapter 2.2 --- Amyloid plaques --- p.8 / Chapter 2.2.1 --- Amyloid precursor protein --- p.8 / Chapter 2.2.2 --- Processing ofAPP --- p.9 / Chapter 2.2.3 --- Amyloid β (Aβ) --- p.12 / Chapter 2.2.4 --- APP mutations and AD --- p.12 / Chapter 2.3 --- Neurofibrillary tangles (NFT) --- p.15 / Chapter 2.3.1 --- Tau --- p.15 / Chapter 2.3.2 --- Tau mutation and neurodegeneration --- p.17 / Chapter 2.4 --- Hypotheses for AD pathology --- p.18 / Chapter 2.4.1 --- Amyloid cascade hypothesis --- p.18 / Chapter 2.4.2 --- Inflammatory hypothesis --- p.20 / Chapter 2.4.2.1 --- Microglia and astrocytes --- p.21 / Chapter 2.4.2.2 --- Inflammatory cytokines --- p.23 / Chapter 2.4.2.3 --- Inflammation and AD --- p.25 / Chapter 2.4.3 --- ApoE hypothesis --- p.27 / Chapter 2.4.3.1 --- Apolipoprotein E --- p.27 / Chapter 2.4.3.2 --- ApoE and AD --- p.28 / Chapter 2.5 --- Theory towards the pathology of AD --- p.30 / Chapter Chapter 3 --- ApoE genotyping --- p.32 / Chapter 3.1 --- Introduction --- p.32 / Chapter 3.2 --- Materials and methods --- p.32 / Chapter 3.2.1 --- Patients and control subjects --- p.32 / Chapter 3.2.2 --- Blood sampling --- p.33 / Chapter 3.2.3 --- DNA genotyping --- p.34 / Chapter 3.2.4 --- Statistical analysis --- p.35 / Chapter 3.3 --- Results --- p.35 / Chapter 3.. --- Discussion --- p.38 / Chapter Chapter 4 --- IL-1β polymorphism in relation to the risk of ADin Chinese --- p.39 / Chapter 4.1 --- Introduction --- p.39 / Chapter 4.2 --- Materials and methods --- p.44 / Chapter 4.2.1 --- Patients and control subjects --- p.44 / Chapter 4.2.2 --- Blood sampling --- p.44 / Chapter 4.2.3 --- DNA genotyping --- p.44 / Chapter 4.2.4 --- Statistical analysis --- p.48 / Chapter 4.3 --- Results --- p.48 / Chapter 4.4 --- Discussion --- p.53 / Chapter Chapter 5 --- TNFα polymorphism in relation to the risk of ADin Chinese --- p.63 / Chapter 5.1 --- Introduction --- p.63 / Chapter 5.2 --- Materials and methods --- p.66 / Chapter 5.2.1 --- Patients and control subjects --- p.66 / Chapter 5.2.2 --- Blood sampling --- p.66 / Chapter 5.2.3 --- DNA genotyping --- p.66 / Chapter 5.2.4 --- Haplotype determination --- p.70 / Chapter 5.2.5 --- Statistical analysis --- p.70 / Chapter 5.3 --- Results --- p.70 / Chapter 5.4 --- Discussion --- p.75 / Chapter Chapter 6 --- LRP8 polymorphism in relation to the risk of ADin Chinese --- p.81 / Chapter 6.1 --- Introduction --- p.81 / Chapter 6.2 --- Materials and methods --- p.87 / Chapter 6.2.1 --- Patients and control subjects --- p.87 / Chapter 6.2.2 --- Blood sampling --- p.87 / Chapter 6.2.3 --- DNA genotyping --- p.87 / Chapter 6.2.4 --- Statistical analysis --- p.89 / Chapter 6.3 --- Results --- p.91 / Chapter 6.4 --- Discussion --- p.98 / Chapter Chapter 7 --- Conclusions and prospects for future work --- p.102 / Chapter 7.1 --- Conclusion --- p.102 / Chapter 7.2 --- Prospects for future work --- p.105 / Reference --- p.106