Cardiac-specific expression of the tetracycline transactivator confers increased heart function and survival following ischemia reperfusion injury.
Cardiac-specific expression of the tetracycline transactivator confers increased heart function and survival following ischemia reperfusion injury.
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DOI：
10.1371/journal.pone.0030129
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
O'Bryan JP
中科院分区：
文献类型：
--
作者：
Elsherif L;Wang X;Grachoff M;Wolska BM;Geenen DL;O'Bryan JP
Mice expressing the tetracycline transactivator (tTA) transcription factor driven by the rat α-myosin heavy chain promoter (α-MHC-tTA) are widely used to dissect the molecular mechanisms involved in cardiac development and disease. However, these α-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 α-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 α-MHC-tTA mice had robust protection against ischemia/reperfusion injury which was not blocked by pharmacological inhibition of PI3Ks with LY294002. Furthermore, α-MHC-tTA mice subjected to coronary artery ligation exhibited significantly reduced infarct size compared to control animals. Our findings reveal that α-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 α-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 α-MHC-tTA model may reveal novel molecular targets for therapeutic intervention during ischemic injury.
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影响因子：
11.4
作者：
Shioi, T;Kang, PM;Izumo, S
通讯作者：
Izumo, S
DOI：
10.1073/pnas.77.10.6119
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
DEBOER, LWV;STRAUSS, HW;BRAUNWALD, E
通讯作者：
BRAUNWALD, E
影响因子：
20.1
作者：
Yu, ZH;Redfern, CS;Fishman, GI
通讯作者：
Fishman, GI
影响因子：
15.9
作者：
Nagoshi, T;Matsui, T;Rosenzweig, A
通讯作者：
Rosenzweig, A
影响因子：
2.7
作者：
Reichelt, Melissa E.;Willems, Laura;Headrick, John P.
通讯作者：
Headrick, John P.