Wan Din. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (leaves 155-175). / ABSTRACT --- p.1 / ACKNOWLEDGMENTS --- p.3 / LIST OF TABLES --- p.5 / LIST OF FIGURES --- p.7 / LIST OF ABBREVIATIONS --- p.8 / Chapter I. --- INTRODUCTION --- p.9 / Chapter I.A. --- Menopause --- p.9 / Chapter I.A.1. --- Definition of the Menopause --- p.9 / Chapter I.A.2. --- Pathophysiology of Ovarian Failure --- p.10 / Chapter I.B. --- Effects of the Menopause --- p.13 / Chapter I B.1. --- Acute Effects --- p.13 / Chapter I.B.2. --- Medium Term Effects --- p.14 / Chapter I.B.3. --- Chronic Effects --- p.15 / Chapter I.B.3.a. --- Osteoporosis --- p.15 / Chapter I.B.3.b. --- Coronary Artery Disease (CAD) --- p.17 / Chapter I.C. --- Management of the Menopause --- p.19 / Chapter I.C.1. --- Hormone Replacement Therapy --- p.21 / Chapter I.C.2. --- Oestrogens --- p.22 / Chapter I.C.2.a. --- Oral Oestrogens --- p.22 / Chapter I.C.3. --- Progestogens --- p.24 / Chapter I.C.3.a. --- Combined Oestrogen and Progestogen Therapy --- p.24 / Chapter I.C.4. --- Complications and Contraindications to Hormone Replacement Therapy --- p.26 / Chapter II. --- LITERATURE REVIEW --- p.34 / Chapter II.A. --- Atherosclerosis --- p.35 / Chapter II.B. --- Risk Factors for Coronary Artery Disease --- p.37 / Chapter II.B.1. --- Age and Sex --- p.38 / Chapter II.B.2. --- Age at Menopause --- p.38 / Chapter II.B.3. --- Family History --- p.38 / Chapter II.B.4. --- Serum Lipids --- p.39 / Chapter II.B.5. --- Blood Pressure --- p.39 / Chapter II.B.6. --- Smoking --- p.40 / Chapter II.B.7. --- Diabetes Mellitus --- p.40 / Chapter II.C. --- The Effect of the Menopause on Risk Factors for Coronary Heart Disease --- p.41 / Chapter II.C.1. --- The Effect of the Menopause on Lipids and Lipoproteins --- p.41 / Chapter II.C.2. --- The Effect of the Menopause on Glucose and Insulin Metabolism --- p.43 / Chapter II.C.3. --- The Effect of the Menopause on Coagulation --- p.44 / Chapter II.C.4. --- The Effect of the Menopause on the Arterial Wall --- p.45 / Chapter II.D. --- The Risk of Coronary Artery Disease After the Menopause --- p.46 / Chapter II.D.1. --- The Effect of the Menopause on Peripheral Vascular Disease (PVD) --- p.47 / Chapter II.E. --- The Effect of the Hormone Replacement Therapy on Coronary Artery Disease Risk --- p.49 / Chapter II.F. --- The Mechanism of Cardioprotection of Oestrogen --- p.63 / Chapter II.F.1. --- The Indirect Effect of the Hormone Replacement Therapy on the Cardiovascular System --- p.64 / Chapter II.F.1.a. --- The Effect on Lipids and Lipoproteins --- p.64 / Chapter II.F.1.b. --- The Effect on Coagulation and Fibrinolysis --- p.66 / Chapter II.F.1.c. --- The Effect on Insulin and Glucose Metabolism --- p.67 / Chapter II.F.2. --- The Direct Effects of the Hormone Replacement Therapy on the Cardiovascular System --- p.67 / Chapter II.F.2.a. --- The Effect of Oestrogen on Vascular Contractility --- p.68 / Chapter II.F.2.b. --- The Effect of Oestrogen on Endothelial Dysfunction --- p.69 / Chapter II.F.2.C. --- Other Possible Direct Actions of Oestrogen --- p.72 / Chapter II.G. --- The Effects of Oestrogen on Blood Flow --- p.73 / Chapter III. --- RESEARCH PLAN --- p.78 / Chapter III.A. --- Formation of Research Hypothesis --- p.78 / Chapter III B. --- Research Hypothesis --- p.80 / Chapter III.C. --- Plan of Studies --- p.81 / Chapter III.C.1. --- Pilot Study --- p.81 / Chapter III.C.2. --- Randomized Controlled Study --- p.81 / Chapter IV. --- METHODOLOGY --- p.84 / Chapter IV.A. --- Pilot Study --- p.84 / Chapter IV.B. --- Study Population --- p.87 / Chapter IV.B.1. --- Recruitment of Cases --- p.88 / Chapter IV.B.1.a. --- Patients' Consent --- p.88 / Chapter IV.B.1.b. --- Method of Recruitment --- p.88 / Chapter IV.B.1.e. --- Research Methodology --- p.89 / Chapter IV.C. --- Ethical Considerations --- p.90 / Chapter IV.D. --- Samples Size Calculation --- p.92 / Chapter IV.E. --- Statistical Analysis --- p.93 / Chapter IV.F. --- Physical Principles of the Measurement of Peripheral Resistance --- p.94 / Chapter IV.F.1. --- The Arterial Analogue Waveform --- p.97 / Chapter IV.F.2. --- Peak Systolic Velocity --- p.98 / Chapter IV.G. --- Measurement of Pulsatility Index --- p.100 / Chapter IV.G.1. --- Establishment of Methodologies Used to Measure Peripheral Blood Flow --- p.105 / Chapter IV.G.2. --- Training of the Investigator --- p.107 / Chapter IV.H. --- Assay for Serum Oestradiol --- p.108 / Chapter IV.H.1. --- Principles --- p.108 / Chapter IV.H.2. --- Reagents --- p.109 / Chapter IV.H.3. --- Sample Dilution --- p.111 / Chapter IV.H.4. --- Calibration --- p.112 / Chapter IV.H.5. --- Quality Control --- p.112 / Chapter IV.H.6. --- Assay Validation --- p.113 / Chapter V. --- RESULTS --- p.115 / Chapter V.A. --- Pilot Study --- p.115 / Chapter V.B. --- Study Population --- p.118 / Chapter V.B.1. --- Characteristics of the Patients at Recruitment --- p.120 / Chapter V.B.2. --- Doppler Measurements --- p.123 / Chapter V.B.3. --- Pulsatility Index and Serum Oestradiol --- p.135 / Chapter VI. --- DISCUSSION --- p.137 / Chapter VI.A. --- Overview --- p.132 / Chapter VI.A.1. --- The Pilot Study --- p.133 / Chapter VI.B. --- Study Population --- p.136 / Chapter VI.C. --- Doppler Ultrasound as a Measurement of Vascular Resistance and Blood Flow --- p.142 / Chapter VI.C.1. --- Reliability of Doppler Study --- p.143 / Chapter VI.D. --- Pulsatility Index and Hormone Replacement Therapy --- p.146 / Chapter VI.E. --- Effects of Oestrogen on Pulsatility Index --- p.150 / Chapter VI.F. --- Conclusions --- p.152 / Chapter VI.G. --- Future Directions --- p.153 / REFERENCES --- p.155 / APPENDIX1 --- p.176

心臟病目前仍然是最普遍的威脅人類生命安全的三大病因之一。同西藥相比, 傳統中醫藥具有多靶點，協同作用及小副作用等特性。在中藥歷史中， 丹參和葛根這兩種草藥經常出現在中藥方劑用於治療心血管相關的疾病，已有幾千年的歷史。 我們實驗室發現了一個丹參葛根湯劑具有保護動脈粥樣硬化病人心臟功能的作用，並且可以使收縮的大鼠大動脈舒張的作用。 本研究主要通過舒張豬冠狀動脈，提高大鼠對抗過氧化和離子擾動能力以及提高血管增生四個方面探討丹參葛根複方水提物 (質量比7:3) (DG配方)對血管的作用以提供其治療心血管疾病的藥理基礎。 / 在本研究的第一部， 我們主要探討了DG配方對缺血再灌注損傷的心臟及其心肌細胞的保護作用。我們發現DG配方明顯抑制了心臟損傷相關的肌酸激酶和乳酸脫氫的釋放。同時DG配方顯著促進了再灌注後冠狀動脈內血流量速度和收縮力度的恢復。這些結果說明DG配方可以保護缺血再灌注心臟並且有效促進其功能恢復。我們還觀察了長期給大鼠用DG配方14天後其心臟在缺血再灌注中的表現。類似於再灌注時給藥的結果，DG配方同樣抑制了損傷酶的釋放並且有效促進了冠狀動脈內血流量速度和收縮力度的恢復。 / 同時，在缺氧再灌注離體細胞模型中，我們發現DG配方明顯抑制了缺氧再灌注損傷帶來的細胞死亡。流式細胞儀分析結果表明，藥物處理組中的凋亡類的細胞明顯比對照組中少主要通過抑制促凋亡的caspase3表達明以及促進抗凋亡的Bcl2表達升高。DG配方減少了心肌細胞內細胞色素c從線粒體中釋放明顯以及抑制了線粒體去極化。這說明DG配方也保護了線粒體的膜的完整性，從而確保線粒體功能進而保證細胞的能量系統穩定。最有意思的是DG配方可以直接抑制缺氧再灌注相關的兩條通路, 它不僅抑制活性氧化物質的釋放, 同時也抑制了再灌注後鈣離子的累積。總之，DG配方以抗氧化和抗離子擾動的方式保護了在缺血缺氧再灌注損傷中心臟和心肌細胞的結構和功能。 / 第二部分的研究是關於DG配方對從豬心臟上分離的左冠狀動脈前室間支 (左前降支) 血管的作用及其內在的機制，我們的結果表明對由U46619引起的冠狀動脈血管收縮DG配方表現了濃度依賴的舒血管作用。而該作用並非依賴于內皮細胞及其釋放的舒張血管因數一氧化氮和前列腺素類似物環素和大部分的鉀離子通道。其中只有內向整合鉀離子通道部分參與了舒血管的過程。肌球蛋白輕鏈的磷酸化明顯被DG配方抑制，但是RhoA 的活性並沒有受其影響。鈣離子引發的血管收縮則被DG配方濃度依賴性的受到抑制。這部分的研究證明瞭DG配方主要通過類似鈣離子通道拮抗劑作用抑制鈣離子進入到血管平滑肌細胞減少肌球蛋白磷酸化達到舒張血管的作用。結果說明DG配方可以作為一種安全的藥物用於治療心血管疾病特別是高血壓和心絞痛。 / 本研究的第三部分是關於DG配方的促血管增生的作用。我們發現DG配方可以明顯促進斑馬魚的腸下動脈的出芽並且促進血管增生相關基因的表達，血管內皮細胞生長因數及其受體的mRNA表達。內皮細胞是血管增生的基礎。所以我們利用人源微血管內皮細胞檢測了DG配方在細胞的增生，遷移，分化和形成血管方面的影響以解釋它在斑馬魚中促進血管增生的作用機理。結果發現，DG配方明顯促進了該種內皮細胞的增殖，遷移和形成管狀結構。 / 綜上所述，DG配方可以通過舒張血管，抗氧化，抗離子紊亂和促進血管增生提供心血管保護功能。DG配方通過螯合活性氧化物質和抑制鈣離子的累積保護了因缺血再灌注引起的心臟損傷，說明DG配方可以作為手術的輔助藥物減少心臟病人在缺血再灌注過程中受到的損傷。它以拮抗L型鈣離子通道方式減少鈣離子進入到血管平滑肌細胞來舒張收縮的冠狀動脈血管。說明DG配方可以用於治療高血壓和心絞痛等心臟病。另外DG配方也可以促進血管增生，可用于心肌梗死病人促進其心臟血管系統重建，本研究對於未來臨床實驗具有重要的參考價值。 / Coronary heart diseases (CHD) are one of the most prevalent causes of premature death all over the world. In contrast to western medicine, traditional Chinese medicine (TCM) has shown the benefit of multi-targeting and synergism to treat CHD. Two kinds of Chinese herbs, Danshen (Radix Salviae Miltiorrhiza) (D) and Gegen (Radix Puerariae Lobatae) (G) always present on the TCM formula for treating heart disease. We found a useful formula of Danshen and Gegen decoction with weight ratio of 7:3 (DG) exerting properties of improving the heart function in patient with atheroslcerosis and providing vasodiation and antioxidant protection on the rat cardiovascular system. The present study was designed to evaluate the effects of DG on the vascular activity by its properties on antioxidant and anti-ion stunning to inhibiting the ischemia and reperfusion injury, vasodilation effect on pig coronary artery and angiogenesis effect on zebrafish model. / In the first part of the study, we explored protective effect of DG on rat hearts and cardiomyocytes after ischemia-reperfusion and hypoxia-reoxygenation injury. Comparing to control group, the release of creatine kinase (CK) and lactate dehydrogenase (LDH) significantly decreased in the DG treated groups in a dose-dependent manner. The recovery percentage of coronary flow and contractile force in the DG was higher than that in the control group. These results suggested that DG dose-dependently improved the heart function after ischemia and reperfusion injury in a dose-dependent manner. We also examined chronic effect of DG (14 days pretreatment) on rat heart with ischemia and reperfusion injury. DG induced rat heart with high potential to deal with I/R injury, less damaged enzymes release and high recovery percentage of heart function recovery. / In the cell hypoxia and reoxygenation model, DG significantly inhibited the cell death after H/R treatment with bcl2 expression increase and caspase3 expression decrease. DG also reversed the H/R-induced mitochondrial depolarization and inhibited cytochrome c diffusing out of mitochondria, which confirmed DG anti-apoptosis activity. DG also was found to significantly decrease the intracellular calcium accumulation and reactive oxygen species release within H9c2. / In the second part of present study, results revealed that DG elicited a concentration-dependent relaxation of U46619-preconstricted porcine coronary artery. DG-induced relaxation responses were not altered by the presence of endothelium-related dilator inhibitors, most potassium channel blockers, GMP and AMP pathway inhibitors and endothelium removal. Ba²⁺ (an inward rectifier K⁺ channel blocker) slightly attenuated DG-induced relaxation. The protein expression of phosphorylated myosin light chain (MLC) was inhibited by DG in a concentration-dependent manner whereas the activity of RhoA was not modified. Ca²⁺-induced contraction of coronary artery was inhibited by DG in a concentration-dependent fashion. DG acted as an antagonist of calcium channel inducing the porcine artery dilation. / The third part of the present study is about the pro-angiogenic effect of DG. We found that DG dose-dependently induced zebrafish sub-intestinal vessel sprouting and increased the mRNA expression of vascular endothelial growth factor (VEGF) and its receptors. To explore the underlying mechanism, we also examined the proangiogenic effect of DG on the angiogenesis of endothelial cells. The results showed that DG induced the HMEC-1 proliferation, migration and forming tube. / In conclusion, we found that DG could provide cardiac and cardiovascular protection by its multiple targets. It prevented heart injuries after ischemia or hypoxia and reperfusion through scavenging ROS and inhibiting calcium accumulation. Moreover, it mainly acts as an antagonist of L-type calcium channel to relax the contracted LAD vessel. It also exerted property of inducing angiogenesis in vivo and in vitro. Therefore, DG would be useful for treating coronary artery disease depending on its multiple targets. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Hu, Fan. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 170-215). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / Chapter 1 --- Intorduction --- p.1 / Chapter 1.1 --- Cardiovascular system and coronary artery diseases --- p.1 / Chapter 1.1.1 --- The cardiovascular system --- p.1 / Chapter 1.1.2 --- Contraction and relaxation of the vascular myocyte in arteries --- p.4 / Chapter 1.1.2.1 --- Ultrastructure of the vascular myocyte --- p.4 / Chapter 1.1.2.2 --- Contraction mechanisms of vascular myocyte --- p.5 / Chapter 1.1.2.3 --- Relaxation mechanisms of vascular myocyte --- p.7 / Chapter 1.1.3 --- Chronic coronary heart disease --- p.9 / Chapter 1.2 --- The way to treat chronic CAD --- p.11 / Chapter 1.2.1 --- Angiogenesis --- p.11 / Chapter 1.2.2 --- Clinical surgery for treating CAD --- p.13 / Chapter 1.2.2.1 --- Three common surgeries for treating CAD --- p.13 / Chapter 1.2.2.2 --- Ischemia and reperfusion (I/R) injury in surgeries --- p.15 / Chapter 1.2.3 --- Drugs for treating CAD --- p.19 / Chapter 1.2.3.1 --- Western medicine therapy in CAD --- p.19 / Chapter 1.2.3.2 --- Traditional Chinese Medicine treatment in CAD --- p.20 / Chapter 1.3 --- Aims of studies --- p.28 / Chapter 2 --- Materials and Methods --- p.29 / Chapter 2.1 --- Solutions and Materials --- p.29 / Chapter 2.1.1 --- Solutions --- p.29 / Chapter 2.1.2 --- Chemicals and enzymes --- p.36 / Chapter 2.2 --- Methods --- p.38 / Chapter 2.2.1 --- Herbal preparation --- p.38 / Chapter 2.2.2 --- Identification and quantification of chemical markers in Danshen and Gegen decoction (DG) --- p.38 / Chapter 2.2.3 --- Assay development for the determination of the DG marker compounds in rat plasma --- p.40 / Chapter 2.2.4 --- Isolation of pig left anterior descending coronary artery --- p.44 / Chapter 2.2.5 --- Isometric tension measurement --- p.45 / Chapter 2.2.6 --- Langendorff related experiment --- p.50 / Chapter 2.2.7 --- Cell culture of H9c2 cells --- p.54 / Chapter 2.2.8 --- Cell viability assay (MTT assay) --- p.56 / Chapter 2.2.9 --- Cell proliferation measurement --- p.57 / Chapter 2.2.10 --- Hypoxia and reperfusion cell model (H9c2) --- p.58 / Chapter 2.2.11 --- Determination of cell apoptosis with Annexin VFITC and PI double staining --- p.59 / Chapter 2.2.12 --- Measurement of mitochondria depolarization --- p.61 / Chapter 2.2.13 --- Measurement of ROS release --- p.63 / Chapter 2.2.14 --- Measurement of calcium localization in H9c2 cells by fluo4 dye and confocal microscopy --- p.64 / Chapter 2.2.15 --- Extraction of proteins from tissue, cell and subcellular fractions --- p.65 / Chapter 2.2.16 --- Western blot assay --- p.67 / Chapter 2.2.17 --- Human microvascular endothelial cells (HMEC1) cell culture --- p.68 / Chapter 2.2.18 --- Cell cycle analysis by PI staining --- p.69 / Chapter 2.2.19 --- Scratch assay for HMEC1cells migration --- p.70 / Chapter 2.2.20 --- Tube formation assay --- p.71 / Chapter 2.2.21 --- Vessel sprouting of Zebrafish --- p.72 / Chapter 2.2.22 --- Real time PCR --- p.74 / Chapter 2.2.23 --- Statistical analysis --- p.76 / Chapter 3 --- Chapter 3 Cardiac protection of Danshen and Gegen decoction in hypoxia/ischemia and reperfusion induced injury --- p.77 / Chapter 3.1 --- Introduction --- p.77 / Chapter 3.2 --- Results --- p.81 / Chapter 3.2.1 --- Cytotoxicity of DG --- p.81 / Chapter 3.2.2 --- The morphology alteration of H9c2 after H/R treatment --- p.83 / Chapter 3.2.3 --- Effect on H H9c2 cell survival after H/R treatment --- p.84 / Chapter 3.2.4 --- Effect on membrane skeleton of H9c2 cells with H/R injury --- p.86 / Chapter 3.2.5 --- Effect on the apoptosis in H9c2 cells induced by H/R injury --- p.88 / Chapter 3.2.6 --- Effect on cytochrome c release from mitochondria of damaged H9c2 cells --- p.92 / Chapter 3.2.7 --- Effect on mitochondria depolarization of H9c2 after H/R treatment --- p.94 / Chapter 3.2.8 --- Effect on reactive oxidant species (ROS) release --- p.96 / Chapter 3.2.9 --- Effect on calcium accumulation within H9c2 in the reperfusion phase --- p.98 / Chapter 3.2.10 --- Effect on heart functions of rat hearts with I/R injury (acute effect) --- p.101 / Chapter 3.2.11 --- Effect on heart function in rats with I/R injury (chronic effect) --- p.107 / Chapter 3.3 --- Discussion --- p.113 / Chapter 4 --- Chapter 4 Vasodilation effects of Danshen and Gegen decoction in porcine coronary artery and its underlying mechanism --- p.118 / Chapter 4.1 --- Introduction --- p.118 / Chapter 4.2 --- Results --- p.121 / Chapter 4.2.1 --- Investigations of endothelium dependent and independent mechanisms --- p.121 / Chapter 4.2.2 --- Effects on cAMP and cGMP pathway --- p.121 / Chapter 4.2.3 --- Effects on potassium channel opening --- p.121 / Chapter 4.2.4 --- Effects on calcium induced contraction and calcium sensitization --- p.122 / Chapter 4.2.5 --- Effects on MLC phosphorylations --- p.123 / Chapter 4.3 --- Discussion --- p.132 / Chapter 5 --- Chapter 5 In vitro and in vivo angiogenic effects of DG --- p.138 / Chapter 5.1 --- Introduction --- p.138 / Chapter 5.2 --- Results --- p.140 / Chapter 5.2.1 --- Effect on subintestinal vessels sprouting in the zebrafish embryo --- p.140 / Chapter 5.2.2 --- Effect on the transcription and expression of VEGFA and VEGF receptors -- Flt1 and KDR/Flk2 --- p.143 / Chapter 5.2.3 --- Effect on HMEC1 proliferation --- p.145 / Chapter 5.2.4 --- Effect on cell cycle of HMEC1 --- p.148 / Chapter 5.2.5 --- Effect on cell migration of HMEC1 --- p.151 / Chapter 5.2.6 --- Effect on tube formation of HMEC1 --- p.154 / Chapter 5.3 --- Discussion --- p.157 / Chapter 6 --- Chapter 6 Conclusions and future work --- p.160 / Chapter 6.1 --- Cardiac protection of DG in the I/R and H/R injury --- p.160 / Chapter 6.2 --- Vasodilation effect of DG on the porcine coronary artery --- p.165 / Chapter 6.3 --- Angiogenic effect of DG in vivo and in vitro --- p.167 / Chapter 6.4 --- Overall conclusion of the study --- p.169 / Chapter 7 --- References --- p.170

Yam Wing Sze. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 154-160). / Abstracts in English and Chinese. / Abstract English --- p.i / Chinese --- p.iii / Acknowledgments --- p.v / Table of contents --- p.vii / List of Tables --- p.x / List of Figures --- p.xi / List of Abbreviations --- p.xvi / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Chinese Medicine and Western Medication --- p.1 / Chapter 1.2 --- Chinese Medicine and Compound Formula --- p.2 / Chapter 1.3 --- Cardiovascular disease (CVD) and atherosclerosis --- p.6 / Chapter 1.4 --- General Research Objectives --- p.19 / Chapter Chapter 2 --- Establishment of compound formulation and Extract Preparation --- p.21 / Chapter 2.1 --- Formulation searched from Chinese Pharmacopoeia --- p.21 / Chapter 2.2 --- Aqueous extract preparation --- p.25 / Chapter 2.2.1 --- Materials and Methods --- p.25 / Chapter 2.2.2 --- Discussion --- p.27 / Chapter Chapter 3 --- Vasodilation study --- p.28 / Chapter 3.1 --- Vascular Smooth Muscle Contraction and Relaxation --- p.28 / Chapter 3.2 --- Endothelium and Vasodilation --- p.30 / Chapter 3.3 --- Vasodilation in organ bath --- p.32 / Chapter 3.3.1 --- Materials and Methods --- p.32 / Chapter 3.3.2 --- Results --- p.35 / Chapter 3.3.3 --- Discussion --- p.40 / Chapter 3.4 --- Endothelium dependent vasodilation --- p.40 / Chapter 3.4.1 --- Materials and Methods --- p.43 / Chapter 3.4.2 --- Results --- p.45 / Chapter 3.4.3 --- Discussion --- p.54 / Chapter 3.5 --- Adrenoceptor and vasodilation --- p.55 / Chapter 3.5.1 --- Materials and Methods --- p.57 / Chapter 3.5.2 --- Results --- p.58 / Chapter 3.5.3 --- Discussion --- p.62 / Chapter 3.6 --- Potassium Channels and Vasodilation --- p.63 / Chapter 3.6.1 --- Materials and Methods --- p.65 / Chapter 3.6.2 --- Results --- p.67 / Chapter 3.6.3 --- Discussion and Summary --- p.77 / Chapter 3.7 --- Potential active components from Fenge and Danshen --- p.82 / Chapter 3.7.1 --- Materials and Methods --- p.82 / Chapter 3.7.2 --- Results --- p.83 / Chapter 3.7.3 --- Discussion --- p.87 / Chapter Chapter 4 --- Comparison of Fenge and Yege --- p.88 / Chapter 4.1 --- Vasodilative effects of Fenge and Yege --- p.89 / Chapter 4.1.1 --- Materials and Methods --- p.89 / Chapter 4.1.2 --- Results --- p.89 / Chapter 4.1.3 --- Discussion --- p.101 / Chapter 4.2 --- The comparison of antioxidative effect between Yege and Fenge --- p.104 / Chapter 4.2.1 --- Red blood cell hemolysis model --- p.106 / Chapter 4.2.1.1 --- Materials and Methods --- p.106 / Chapter 4.2.1.2 --- Results --- p.108 / Chapter 4.2.1.3 --- Discussion --- p.110 / Chapter 4.2.2 --- Ischemia-reperfusion on Langendroff --- p.112 / Chapter 4.2.2.1 --- Materials and Methods --- p.114 / Chapter 4.2.2.2 --- Results --- p.117 / Chapter 4.2.2.3 --- Discussion --- p.125 / Chapter Chapter 5 --- Comparison of Chemical Profiles of Fenge and Yege --- p.127 / Chapter 5.1 --- The application of HPLC --- p.127 / Chapter 5.2 --- HPLC standardization --- p.129 / Chapter 5.2.1 --- Materials and Methods --- p.132 / Chapter 5.2.2 --- Results --- p.133 / Chapter 5.2.3 --- Discussion --- p.144 / Chapter Chapter 6 --- "Summaries, Discussion and prospects" --- p.146 / Chapter 6.1 --- Summaries and Discussion --- p.146 / Chapter 6.2 --- Prospects --- p.148 / Chapter 6.2.1 --- "Cardiovascular tonic effect of pure compounds, extracts with difference solvents and their vasodilative mechanism." --- p.148 / Chapter 6.2.2 --- Macrophage Foam Cell and Atherosclerosis --- p.149 / Chapter 6.2.3 --- The D:F (7:3) and D:Y (7:3) compound formulae capsule with GMP --- p.152 / References --- p.154

Clopidogrel is an antiplatelet drug prescribed to prevent stent thrombosis after a percutaneous coronary intervention (PCI). Previous evidence suggests that some widely prescribed statins may inhibit the antiplatelet effects of clopidogrel via competitive metabolism of its activating enzyme cytochrome P450 3A4 (CYP3A4). / The objective was to investigate the possibility of an interaction post-PCI between statins and clopidogrel. / We carried out a population-based cohort study identifying 10,491 patients using clopidogrel post-PCI (2001-2004). The outcome was a composite of death of any cause, myocardial infarction, unstable angina, repeat revascularization, and cerebrovascular events. We found that co-prescription of CYP3A4-metabolized statins (hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.79-1.15), or non-CYP3A4-metabolized statins (HR 0.82, 95% CI 0.63-1.07) with clopidogrel was not associated with increase in adverse outcomes. / We observed no evidence of interaction between clopidogrel and statins in a large population cohort of PCI patients, suggesting unlikelihood of an important interaction.

No description available.

Tam Wing Yin. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 82-100). / Abstracts in English and Chinese. / English abstrac --- p.I / 中文摘要 --- p.VI / Glossary --- p.X / Chapter Chapter 1. --- Background: / Chapter 1.1. --- Coronary heart disease in Hong Kong --- p.1 / Chapter 1.2. --- Coronary heart disease and atherosclerosis --- p.2 / Chapter 1.3. --- Pathogenesis of atherosclerosis --- p.2 / Chapter 1.4. --- Risk factors for atherosclerosis --- p.5 / Chapter 1.5. --- Homocysteine --- p.6 / Chapter 1.6. --- Folate --- p.10 / Chapter 1.7. --- Vitamin B12 --- p.13 / Chapter 1.8. --- Adhesion Molecules --- p.14 / Chapter 1.9. --- Phytoestrogen --- p.17 / Chapter 1.10. --- Secondary prevention of coronary artery disease --- p.20 / Chapter Chapter 2. --- "Heart disease, Danshen and Gegen in Chinese medicine" / Chapter 2.1. --- The record of Cardiac symptoms in Chinese Medicine --- p.24 / Chapter 2.2. --- Danshen (Salvia Miltriorrhiza) --- p.25 / Chapter 2.3. --- Gegen (Radix Pueraria) --- p.28 / Chapter Chapter 3. --- Surrogate atherosclerotic markers / Chapter 3.1. --- Flow-mediated dilatation of brachial artery (FMD) --- p.31 / Chapter 3.2. --- Carotid intima media thickness (IMT) --- p.32 / Chapter Chapter 4. --- Method / Chapter 4.1. --- Rational of the study --- p.33 / Chapter 4.2. --- Clinical protocol --- p.35 / Chapter 4.3. --- Measurement of plasma homocysteine --- p.38 / Chapter 4.4. --- Measurement of folate and vitamin B12 --- p.40 / Chapter 4.5. --- Measurement of soluble cellular adhesion molecules (CAMs) --- p.41 / Chapter 4.6. --- Measurement of plasma enterolactone --- p.43 / Chapter 4.7. --- Measurement of plasma hs-C-reactive protein --- p.44 / Chapter 4.8. --- Other laboratory tests --- p.45 / Chapter 4.9. --- High resolution ultrasound imaging --- p.46 / Chapter 4.10. --- Statistical analysis --- p.49 / Chapter 4.11. --- My contribution to this joint project --- p.49 / Chapter Chapter 5. --- Results / Chapter 5.1. --- Recruitment and outcomes of subjects --- p.51 / Chapter 5.2. --- Baseline characteristics --- p.53 / Chapter 5.3. --- Medical history and treatment received in the study subjects --- p.54 / Chapter 5.4. --- Safety profiles --- p.55 / Chapter 5.5. --- Severe adverse events --- p.56 / Chapter 5.6. --- Lipid profiles --- p.57 / Chapter 5.7. --- Secondary endpoints --- p.58 / Chapter 5.8. --- Primary endopoints --- p.59 / Chapter 5.9. --- The effect of statin usage on the primary endpoints / Chapter 5.10. --- The major determinant of the change in FMD by multivariate logistic regression / Chapter 5.11. --- Progress of lipid profiles and primary endpoints in the open label phase / Chapter Chapter 6. --- Discussion / Chapter 6.1. --- Brachial FMD --- p.66 / Chapter 6.2. --- Carotid IMT --- p.69 / Chapter 6.3. --- Brachial GTN --- p.70 / Chapter 6.4. --- Lipid-lowering effect --- p.72 / Chapter 6.5. --- Phytoestrogen --- p.72 / Chapter 6.6. --- Folate --- p.73 / Chapter 6.7. --- Vitamin B12 and glucose --- p.76 / Chapter 6.8. --- Summary of possible anti-atherogenic mechanism of D&G --- p.76 / Chapter 6.9. --- Placebo effect --- p.77 / Chapter 6.10. --- Safety profile --- p.77 / Chapter 6.11. --- Limitation of the study and suggestion of solution --- p.77 / Chapter 6.12. --- Suggestions and ummary of the future work --- p.79 / Chapter Chapter 7. --- Conclusions --- p.81 / References --- p.82

Coronary heart diseases (CHD) remain the most prevalent cause of premature death. Ischemic hearts often result from coronary vasculature occlusion. Significant efforts have been made for the treatment of CHD, including medications and surgical procedures. Currently there are still no effective drugs or therapeutics available for the treatment of the disease. Growing new coronary vessels to naturally bypass narrowed/occluded arteries or forming sufficient collaterals to the ischemic region would lead to substantially improved blood perfusion and correction of ischemia. However, this aim remains a theoretical ideal due to the negligible ability to grow new coronary vessels even with current advances in therapeutic angiogenesis. In the present study, we have isolated and identified an active fraction of Geum japonicum (AFGJ) showing significant activity in induction of efficient coronary angiogenesis and heart function improvement. / In addition, proteomics methods were applied to investigate the protein alterations in CHD ischemic hearts and HUVECs. Two dimensional polyacrylamide gel electrophoresis (2-D PAGE) of the heart tissues of CHD rats showed 16 differentially expressed spots compared with sham and vehicle hearts, of which 8 were identified. Furthermore, 11 identified proteins of HUVECs treated with AFGJ or Angio-G at different time points were also observed by 2-D PAGE. The majority of identified proteins was found to be involved in the process of energy metabolisms. / In conclusion, these results have demonstrated therapeutic properties of AFGJ to induce early reconstitution of damaged coronary vasculature through both angiogensis and vasculogenesis. AFGJ treatments may provide a novel therapeutic modality for effective treatment of ischemic heart diseases. / The therapeutic effect of AFGJ on CHD through reconstitution of partially occluded coronary vessels in CHD animal models was demonstrated with underlying signaling mechanisms identified. Briefly, AFGJ could promote the proliferation of human umbilical vein endothelial cells (HUVECs) in vitro and the growth of new blood vessels or coronary collaterals in CHD models after 2-week treatment. The number of newly formed coronary vessels in treated hearts was more than that of vehicle treated hearts, as indicated by both MicroCT and histology analysis. Echocardiography studies demonstrated significant improvement of heart functions 2 weeks after treatment with AFGJ. Furthermore, ECG measurements showed that the altered ST segment in AFGJ treated CHD models almost had full recovery to a normal level while rats in the vehicle group consistently suffered from heart ischemia. Moreover, the results of MicroCT reconstruction directly demonstrated the reconstitution of the damaged coronary vessels with newly formed functional coronary collaterals, as illustrated by more blood vessels density (AFGJ vs vehicle [%]: 4.5+/-0.5 vs 2+/-0.35) and more branching points (AFGJ vs vehicle: 0.94+/-0.07 vs 0.65+/-0.10). These data suggest that AFGJ treatment significantly corrects the ischemia of the affected regions of the heart. / We also explored possible mechanisms underlying the effect of AFGJ. Firstly, AFGJ could induce mesenchymal stem cell (MSC) differentiation into vascular endothelial cells and the differentiated MSCs were involved in the tube formation. Secondly, Angio-G, the component derived from AFGJ, was able to stimulate significant proliferation of HUVECs in a dose dependent manner. Thirdly, in our tube-like capillary formation test of HUVECs in vitro, the length of formed tubes was greatly amplified with increasing concentration of Angio-G. Furthermore, the total length of Angio-G induced tubes was significantly reduced with increasing concentrations of AG490, an inhibitor of JAK/STAT pathways indicating possible involvement of the JAK/STAT signaling pathway. / Chen, Hao. / "December 2009." / Source: Dissertation Abstracts International, Volume: 72-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 136-145). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.