| First Author | Feng HZ | Year | 2014 |
| Journal | Physiol Rep | Volume | 2 |
| Issue | 9 | PubMed ID | 25194024 |
| Mgi Jnum | J:232148 | Mgi Id | MGI:5776102 |
| Doi | 10.14814/phy2.12139 | Citation | Feng HZ, et al. (2014) Abnormal splicing in the N-terminal variable region of cardiac troponin T impairs systolic function of the heart with preserved Frank-Starling compensation. Physiol Rep 2(9) |
| abstractText | Abnormal splice-out of the exon 7-encoded segment in the N-terminal variable region of cardiac troponin T (cTnT-DeltaE7) was found in turkeys and, together with the inclusion of embryonic exon (eTnT), in adult dogs with a correlation with dilated cardiomyopathy. Overexpression of these cTnT variants in transgenic mouse hearts significantly decreased cardiac function. To further investigate the functional effect of cTnT-DeltaE7 or DeltaE7+eTnT in vivo under systemic regulation, echocardiography was carried out in single and double-transgenic mice. No atrial enlargement, ventricular hypertrophy or dilation was detected in the hearts of 2-month-old cTnT-DeltaE7 and DeltaE7+eTnT mice in comparison to wild-type controls, indicating a compensated state. However, left ventricular fractional shortening and ejection fraction were decreased in DeltaE7 and DeltaE7+eTnT mice, and the response to isoproterenol was lower in DeltaE7+eTnT mice. Left ventricular outflow tract velocity and gradient were decreased in the transgenic mouse hearts, indicating decreased systolic function. Ex vivo working heart function showed that high afterload or low preload resulted in more severe decreases in the systolic function and energetic efficiency of cTnT-DeltaE7 and DeltaE7+eTnT hearts. On the other hand, increases in preload demonstrated preserved Frank-Starling responses and minimized the loss of cardiac function and efficiency. The data demonstrate that the N-terminal variable region of cardiac TnT regulates systolic function of the heart. |
