Heart failure, as a result of myocardial infarction, is a major cause of mortality in human. The main cause of heart failure is that when adult cardiomyocytes die in the infarct site they do not regenerate. Instead the infract site is replaced by fibroblasts and collagen scar. It is generally believed that cardiomyocytes have terminally differentiated and can not divide to replace cardiomyocytes that have lost following injury. However, recently published data have provided new evidence that there is a small but continuously turnover of cardiomyocytes in the adult heart. These new findings provide a new theory that the heart does possess a limited ability to regenerate. / I also examined the regenerative ability of cardiomyocyte in adult heart. MRL mice were used because previously it has been reported that the cardiomyocyte could proliferate in response to injury. To understand how the cardiomyocytes in the MRL mouse heart, I used a cryo-injury approach. I discovered that the cardiomyoctyes in MRL mouse hearts were capable of dividing shortly after cryo-injury. These MRL hearts healed without scarring in contrast to C57BL/6 control mice. It was discovered that BMP-2, GATA4 and Nkx2.5 were involved in the healing process. The activation of these genes induced the cardiomyocyte to re-enter the cell cycle so that new cardiomyocytes could replace the cell that have been lost in the infarct site. I also discovered that stem cells may also play a minor role in the healing process. / In summary, my research findings revealed that cardiomyocytes regeneration in the heart is a very complex process that involves the participation of many cells and signalling pathway. There findings raise many intriguing and important questions and are worthy of being addressed in the future. / Stem cell therapy has been proposed as a potential treatment for various myocardial diseases. Chen et al. (2004) found small chemical called reversine that could dedifferentiate C2C12 cells to become stem-like cells. In this study, I demonstrated that reversine could inhibit the growth of C2C12 cell. The presence of reversine in cell culture could significantly inhibit muscle-specific genes MyoD, Myogenin and Myf5 expression. These 3 muscle specific transcriptional genes are essential for maintaining muscle differentiation. The down regulation of these gene showed that reversine could dedifferentiate C2C12 cells. We also discovered that reversine-treated C2C12 cells could differentiate into cardiomyocytes when they were cocultured with cardiomyocytes or when transplanted into the infarct site of a cryo-injured heart. / To investigate the regenerative potential of cardiomyoctyes in adult heart, we tried first to uncover the signals that direct post-natal cardiomyocytes to enter into growth arrest and differentiation. In the first part of my study, I established that the cardiomycytes divided extensively in 2 day-old post-natal hearts and that the majority of these cells entered into growth arrest and terminal differentiation at day 13. Comparative proteomic techniques were used in order to identify proteins that might be associated with cardiomyocytes proliferation during terminal differentiation the mouse heart. Several proteins were found to be differently expressed and amongst them was cyclin I protein. Cyclin I was found strongly expressed in 13 day old hearts. The protein is involved in signaling growth arrested in cells. / Liu, Ye. / "November 2006." / Adviser: Lee Ka Ho. / Source: Dissertation Abstracts International, Volume: 68-09, Section: B, page: 5658. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 142-172). / 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, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_343853 |
| Date | January 2006 |
| Contributors | Liu, Ye, Chinese University of Hong Kong Graduate School. Division of Anatomy. |
| 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 (xiii, 175 p. : 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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