| First Author | Elsherif L | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 1 | Pages | e30129 |
| PubMed ID | 22272284 | Mgi Jnum | J:179877 |
| Mgi Id | MGI:5304301 | Doi | 10.1371/journal.pone.0030129 |
| Citation | Elsherif L, et al. (2012) Cardiac-specific expression of the tetracycline transactivator confers increased heart function and survival following ischemia reperfusion injury. PLoS One 7(1):e30129 |
| abstractText | Mice expressing the tetracycline transactivator (tTA) transcription factor driven by the rat alpha-myosin heavy chain promoter (alpha-MHC-tTA) are widely used to dissect the molecular mechanisms involved in cardiac development and disease. However, these alpha-MHC-tTA mice exhibit a gain-of-function phenotype consisting of robust protection against ischemia/reperfusion injury in both in vitro and in vivo models in the absence of associated cardiac hypertrophy or remodeling. Cardiac function, as assessed by echocardiography, did not differ between alpha-MHC-tTA and control animals, and there were no noticeable differences observed between the two groups in HW/TL ratio or LV end-diastolic and end-systolic dimensions. Protection against ischemia/reperfusion injury was assessed using isolated perfused hearts where alpha-MHC-tTA mice had robust protection against ischemia/reperfusion injury which was not blocked by pharmacological inhibition of PI3Ks with LY294002. Furthermore, alpha-MHC-tTA mice subjected to coronary artery ligation exhibited significantly reduced infarct size compared to control animals. Our findings reveal that alpha-MHC-tTA transgenic mice exhibit a gain-of-function phenotype consisting of robust protection against ischemia/reperfusion injury similar to cardiac pre- and post-conditioning effects. However, in contrast to classical pre- and post-conditioning, the alpha-MHC-tTA phenotype is not inhibited by the classic preconditioning inhibitor LY294002 suggesting involvement of a non-PI3K-AKT signaling pathway in this phenotype. Thus, further study of the alpha-MHC-tTA model may reveal novel molecular targets for therapeutic intervention during ischemic injury. |
