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| Content Provider | PubMed Central |
|---|---|
| Author | Suarez, Jorge Wang, Hong Scott, Brian T. Ling, Haiyun Makino, Ayako Swanson, Eric Brown, Joan Heller Suarez, Jorge A. Feinstein, Shera Diaz-juarez, Julieta Dillmann, Wolfgang H. |
| Copyright Year | 2014 |
| Abstract | Ischemic heart disease (IHD) is the single most common cause of death. New approaches to enhance myocardial perfusion are needed to improve outcomes for patients with IHD. Thyroid hormones (TH) are known to increase blood flow; however, their usefulness for increasing perfusion in IHD is limited because TH accelerates heart rate, which can be detrimental. Therefore, selective activation of TH effects is desirable. We hypothesized that cell-type-specific TH receptor (TR) expression can increase TH action in the heart, while avoiding the negative consequences of TH treatment. We generated a binary transgenic (BTG) mouse that selectively expresses TRα1 in endothelial cells in a tetracycline-inducible fashion. In BTG mice, endothelial TRα1 protein expression was increased by twofold, which, in turn, increased coronary blood flow by 77%, coronary conductance by 60%, and coronary reserve by 47% compared with wild-type mice. Systemic blood pressure was decreased by 20% in BTG mice after TRα1 expression. No effects on heart rate were observed. Endothelial TRα1 expression activated AKT/endothelial nitric oxide synthase pathway and increased A2AR adenosine receptor. Furthermore, hearts from BTG mice overexpressing TRα1 that were submitted to 20 min ischemia and 20 min reperfusion showed a 20% decline in left ventricular pressure (LVP) compared with control mice where LVP was decreased by 42%. Studies using an infarction mouse model demonstrated that endothelial overexpression of TRα1 decreased infarct size by 45%. In conclusion, selective expression of TRα1 in endothelial cells protects the heart against injury after an ischemic insult and does not result in adverse cardiac or systemic effects. |
| Related Links | http://dx.doi.org/10.1152/ajpregu.00449.2013 |
| Starting Page | 340 |
| File Format | |
| ISSN | 15221490 |
| e-ISSN | 15221490 |
| Journal | American Journal of Physiology - Regulatory, Integrative and Comparative Physiology |
| Issue Number | 3 |
| Volume Number | 307 |
| Language | English |
| Publisher | American Physiological Society |
| Publisher Date | 2014-08-01 |
| Access Restriction | Open |
| Rights Holder | American Physiological Society |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Physiology (medical) |
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