Furthermore, ACS patients with a high N-terminal pro-B-type natriuretic peptide (NT-proBNP) and a high ROCK activity on admission had a five-fold risk to experience a cardiovascular event, when compared to those with low NT-proBNP and low ROCK activity. In addition, patients with high NT-proBNP and high ROCK activity were also more likely to die or experience a cardiovascular event at two years when comparing to those with high NT-proBNP and low ROCK activity. / In both ACS and CHF study cohorts, all the clinical parameters were recorded and analyzed. / In the first part of this thesis, 176 ACS patients and 51 control subjects were studied. All The patients were enrolled between December 2007 and May 2009 and followed up till 15th March 2010 (mean: 15.4+/-7.6 months, from 0.5 month to 27.5 months). The main outcome measures were all cause mortality, readmission with ACS or congestive heart failure (CHF) at 2 years from presentation. Altogether, there were 23 deaths (13.1%),33 readmissions with ACS (18.8%) and 13 admissions with CHF (7.4%) within 2 years. / Recent studies have shown that ROCK may playa pivotal role in cardiovascular diseases such as vasospastic angina, ischemic stroke, heart failure and metabolic syndrome via its involvement in regulation of vascular tone, endothelial dysfunction, inflammation, and remodeling. Indeed, inhibition of ROCK by statins or other selective inhibitors leads to upregulation and activation of endothelial nitric oxide synthase (eNOS) and reduction of vascular inflammation and atherosclerosis. In this thesis, we hypothesized that ROCK activity is increased in a selected population of patients with acute coronary syndrome (ACS) and congestive heart failure (CHF) and that ROCK activity is able to predict long-term clinical outcomes in these two populations. / Rho/rho-kinase (ROCK) is a serine-threonine protein kinase, which is one of the first immediate downstream targets of RhoA and expressed ubiquitously. ROCK is involved in many cellular functions, such as, cell growth, migration, apoptosis via actin cytoskeleton organization, and gene expression. They regulate cell contraction through serine-threonine phosphorylation of adducin, ezrin-radixin-moesin proteins, LIM kinase, myosin light chain phosphatase, and Sodium-Hydrogen ion (Na/H) exchanger. / The main findings are: ROCK activity was increased in ST elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) and unstable angina (UA) groups when comparing with disease controls and healthy controls. On multivariate analysis, heart failure symptom on presentation, LDL-C level, and number of diseased coronary vessels were independent predictors of ROCK activity in ACS patients. / The ROCK activity in CHF patients was significantly higher than that of the disease control and normal control groups. New York Heart Association (NYHA) class, low left ventricular ejection fraction (LVEF) and high creatinine were independent predictors of the baseline ROCK activity in CHF. In terms of long-term heart failure mortality, ROCK activity was not an independent predictor. However, combining ROCK activity and NT-proBNP provided an incremental value in predicting long-term heart failure mortality over NT-proBNP alone. / Thus, increased ROCK activity is likely involved in cardiovascular diseases and further studies would be helpful to elucidate the potential role of ROCK activity inhibition in cardiovascular diseases. / We also recruited a group of 178 patients with CHF. All the patients were enrolled between December 2007 and January 2009 and followed up until 1st February 2010 (mean: 14.4+/-7.2 months, from 0.5 month to 26 months) or until the occurrence of cardiac death. Forty-five patients died (25.3%) within 2 years follow up. / Dong, Ming. / Adviser: Cheuk Man Yu. / Source: Dissertation Abstracts International, Volume: 73-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 140-164). / 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, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_344778 |
| Date | January 2011 |
| Contributors | Dong, Ming, Chinese University of Hong Kong Graduate School. Division of Medical Sciences. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, theses |
| Format | electronic resource, microform, microfiche, 1 online resource (xviii, 164 leaves : ill.) |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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