Chan, Yuet Wa. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 217-232). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese.

Cheung, Wing Shing David. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 201-217). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Ng, Chun Fai. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 134-150). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgements --- p.vii / Table of Contents --- p.ix / Abbreviations --- p.xii / List of Figures --- p.xv / List of Tables --- p.xviii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- "Introduction to Cardiovascular Disease, Hypertension and Atherosclerosis" --- p.1 / Chapter 1.1.1 --- Cardiovascular Disease --- p.1 / Chapter 1.1.2 --- Hypertension --- p.2 / Chapter 1.1.2.1 --- Background --- p.2 / Chapter 1.1.2.2 --- Causes of Hypertension --- p.3 / Chapter 1.1.2.3 --- Current Western Management and Medication --- p.6 / Chapter 1.1.3 --- Atherosclerosis --- p.9 / Chapter 1.1.3.1 --- Background --- p.9 / Chapter 1.1.3.2 --- Pathogenesis of Atherosclerosis --- p.10 / Chapter 1.1.3.3 --- Current Western Treatment and Medication --- p.12 / Chapter 1.2 --- Selection and Introduction of Current Chinese Medicine Formula --- p.16 / Chapter 1.2.1 --- Cardiac Syndrome in Traditional Chinese Medicine --- p.16 / Chapter 1.2.2 --- Traditional Chinese Medicine as an Complementary or Alternative Medicine --- p.17 / Chapter 1.2.3 --- Selection of TCM Formula from Pharmacopoeia --- p.18 / Chapter 1.2.3.1 --- Compound Formula --- p.18 / Chapter 1.2.4 --- Introduction to Constitutional Herbal Medicine --- p.19 / Chapter 1.2.4.1 --- Danshen (Radix Salviae miltiorrhizae) --- p.19 / Chapter 1.2.4.2 --- Gegen (Radix Puerariae lobatae) --- p.20 / Chapter 1.2.4.3 --- Yanhusuo (Rhizoma Corydalis) --- p.21 / Chapter 1.2.4.4 --- Composition of the Final Formula Used in the Present Study --- p.21 / Chapter 1.2.5 --- Previous work on Danshen-Gegen Formula and its limitations --- p.22 / Chapter 1.3 --- Objectives of the Present Study --- p.25 / Chapter 1.3.1 --- Research Plan --- p.26 / Chapter Chapter 2 --- Experimental Design and General Methodology --- p.27 / Chapter 2.1 --- Source and Authentication of Raw Herbs --- p.27 / Chapter 2.2 --- Materials --- p.29 / Chapter 2.3 --- Ethical Approval --- p.31 / Chapter 2.4. --- General Methods --- p.32 / Chapter 2.4.1 --- Blood Pressure Measurement --- p.32 / Chapter 2.4.2 --- Blood Profile Measurement --- p.33 / Chapter 2.4.3 --- Vascular Reactivity Studies --- p.36 / Chapter 2.5 --- Statistical Analysis --- p.38 / Chapter Chapter 3 --- Anti-hypertensive Studies of Danshen-Gegen Formula on Rat --- p.39 / Chapter 3.1 --- Introduction --- p.39 / Chapter 3.1.1 --- In vivo Anti-Hypertensive Studies --- p.39 / Chapter 3.1.1.1 --- Spontaneously Hypertensive Rat (SHR) --- p.40 / Chapter 3.1.1.2 --- Tail-cuff Blood Pressure Measurement --- p.41 / Chapter 3.1.2 --- Detailed Underlying Mechanistic Studies --- p.42 / Chapter 3.1.2.1 --- Nitric Oxide-mediated Vasodilation --- p.42 / Chapter 3.1.2.2 --- Prostacyclin-mediated Vasodilation --- p.43 / Chapter 3.1.2.3 --- Hyperpolarization-mediated Vasodilation --- p.43 / Chapter 3.1.2.4 --- Endothelium-dependent/-independent Vasodilation --- p.46 / Chapter 3.1.3 --- Long Term Underlying Mechanistic Studies --- p.48 / Chapter 3.2 --- Methods --- p.49 / Chapter 3.2.1 --- In vivo Anti-Hypertensive Studies --- p.49 / Chapter 3.2.2 --- Detailed Underlying Mechanistic Studies --- p.51 / Chapter 3.2.3 --- Long Term Underlying Mechanistic Studies --- p.53 / Chapter 3.2.4 --- Statistical analysis --- p.56 / Chapter 3.3 --- Results --- p.58 / Chapter 3.3.1 --- In vivo Anti-Hypertensive Studies --- p.58 / Chapter 3.3.1.1 --- Preventive Effect in Hypertension --- p.58 / Chapter 3.3.1.2 --- Therapeutic Effect in Hypertension --- p.62 / Chapter 3.3.2 --- Detailed Underlying Mechanistic Studies --- p.66 / Chapter 3.3.2.1 --- DG extract-induced Vasodilation --- p.66 / Chapter 3.3.2.2 --- Endothelium-independent Vasodilation --- p.67 / Chapter 3.3.2.3 --- Nitric Oxide-mediated Vasodilation --- p.68 / Chapter 3.3.2.4 --- Prostacyclin-mediated Vasodilation --- p.69 / Chapter 3.3.2.5 --- Hyperpolarization-mediated Vasodilation --- p.70 / Chapter 3.3.3 --- Long Term Underlying Mechanistic Studies --- p.74 / Chapter 3.4 --- Discussion --- p.79 / Chapter Chapter 4 --- Anti-atherosclerosis Studies of Danshen-Gegen Formula in Rabbits --- p.89 / Chapter 4.1 --- Introduction --- p.89 / Chapter 4.1.1 --- Intima-Media Thickening --- p.89 / Chapter 4.1.2 --- Effect of High Cholesterol Diet in Rabbit --- p.90 / Chapter 4.1.3 --- Thiobarbituric Acid Reactive Substances --- p.91 / Chapter 4.2 --- Methods --- p.93 / Chapter 4.2.1 --- Pilot Study for Establishment of Experimental Protocol --- p.93 / Chapter 4.2.2 --- Effect of DG extract on Intima-media Thickening --- p.97 / Chapter 4.2.3 --- Statistical analysis --- p.99 / Chapter 4.3 --- Result --- p.100 / Chapter 4.3.1 --- Study of the Anti-atherosclerosis Effect of DG extract - First Run --- p.100 / Chapter 4.3.2 --- Study of the Anti-atherosclerosis Effect of DG extract - Second Run --- p.108 / Chapter 4.4 --- Discussion --- p.117 / Chapter Chapter 5 --- General Discussion and Conclusion --- p.122 / Chapter 5.1 --- Significance of the Study --- p.122 / Chapter 5.2 --- Limitations and Future work --- p.127 / Chapter 5.3 --- Clinical Implication of the Use of the DG Preparations for Patients with CVD --- p.132 / References --- p.134

Indiana University-Purdue University Indianapolis (IUPUI) / Cardiovascular disease is the number one cause of death for Americans. New treatments are needed for serious conditions like atherosclerosis, as it can lead to stroke and heart attack. Many types of cells contribute to the progression of cardiovascular disease, including smooth muscle cells that comprise the middle layers of arteries. Inappropriate growth and migration of smooth muscle cells into the lumen of arteries has been implicated in vascular diseases. Death associated protein kinase (DAPK) is a protein that has been found to regulate the survival and migration of cancer cells, but has not been well characterized in vascular cells. The objective of this work was to determine the signaling pathways that DAPK regulates in smooth muscle cells. These studies have focused on smooth muscle cells isolated from human coronary arteries (HCASM cells). We have determined that HCASM cells depleted of DAPK exhibit more rapid migration, showing that DAPK negatively regulates migration of vascular cells. Results from a focused RT-PCR array identified matrix metalloproteinase 9 (MMP9) as a gene that is increased in cells depleted of DAPK. MMP9 is an important enzyme that degrades collagen, a component of the extracellular matrix through which smooth muscle cells migrate during atherosclerosis. We found that DAPK regulates phosphorylation of the NF-kappa B transcription factor p65 at serine 536, a modification previously found to correlate with increased nuclear levels and activity of p65. In DAPK-depleted HCASM cells, there was more phosphorylation of p65, which causes increased MMP9 promoter activity. Additional experiments were conducted using transgenic mice in which the DAPK gene has been deleted. By studying these mice, we have determined that under some circumstances DAPK augments maximal MMP9 levels in mouse carotid arteries which have been injured by ligation surgery via other signaling pathways. MMP9 has been previously implicated as a protein that promotes vascular diseases such as atherosclerosis. Our research in identifying DAPK as a regulator of MMP9 expression identifies a new target for treatment of vascular diseases like atherosclerosis.