Cardiovascular disease remains the number one cause or mortally in the western world. Heart failure is the most rapidly growing cardiovascular disease (Hobbs, 2004; Levy, et al., 2002). Heart failure, by definition, is progressive deteriorating function of the heart due to progressive cardiac myocytes loss. Though after decades of endeavor of searching the pathophysiology and treatments for heart failure, it remains highly lethal. Therefore, it is vital to find novel therapies to help treat such chronic disease. Replace the lost cardiomyocyte with new ones could restore cardiac function and reduce mortality. The purpose of this study is to investigate on how TTCCs (T-type calcium channels) affect cardiomyocyte proliferation. In mice after birth, the major TTCC expressed in the heart is Cav3.1/α1G, and therefore we used Cav3.1/α1G transgenic (TG), knockout (-/-) and wild type mice respectively to define the role of TTCC in cardiomyocyte proliferation. In neonatal mouse ventricular myocyte (NMVMs) right after birth, there is almost no TTCC after birth in α1G-/- NMVMs, whereas there are around 35% NMVMs in wild type (WT) show TTCC. On day 7 after birth, there are no T-type calcium currents in both α1G-/- NMVMs and WT NMVMs. Using BrdU, a DNA synthesis marker, we identified plenty of BrdU positive cardiomyocyte during the first seven days after birth. Cardiomyocyte is special due to its double nucleation property. Our cell cycle studies showed that there is significant difference in cell cycle distribution between α1G-/- and WT NMVMs on day seven after birth. Significantly more NMVMs are arrested in G1 phase in α1G-/-, compared to WT NMVMs. Even until 2 month old, there are still significantly more mono-nucleated cardiomyocyte in α1G-/- than in WT. In conclusion, all these evidence showed that blocking T-type calcium channel could partially prevent binucleation from happening and stop cardiomyocytes withdrawal from cell cycle. Mononucleated cardiomyocyte is still able to proliferate. Hence, mononucleated cardiomyocytes in adult still have potential to proliferation because these cardiomyoctes are arrested in their cell-cycle before their terminal differentiation, which could offer a novel approach for cardiac repair. / Physiology
| Identifer | oai:union.ndltd.org:TEMPLE/oai:scholarshare.temple.edu:20.500.12613/3780 |
| Date | January 2012 |
| Creators | Wang, Fang |
| Contributors | Houser, Steven R., Chen, Xiongwen, Scalia, Rosario, Sabri, Abdelkarim, Wang, Hong, 1956 September 19- |
| Publisher | Temple University. Libraries |
| Source Sets | Temple University |
| Language | English |
| Detected Language | English |
| Type | Thesis/Dissertation, Text |
| Format | 78 pages |
| Rights | IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available., http://rightsstatements.org/vocab/InC/1.0/ |
| Relation | http://dx.doi.org/10.34944/dspace/3762, Theses and Dissertations |
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