| First Author | Rindler TN | Year | 2013 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 304 |
| Issue | 8 | Pages | H1147-58 |
| PubMed ID | 23436327 | Mgi Jnum | J:196689 |
| Mgi Id | MGI:5489028 | Doi | 10.1152/ajpheart.00594.2012 |
| Citation | Rindler TN, et al. (2013) Knockout of the Na,K-ATPase alpha2-isoform in cardiac myocytes delays pressure overload-induced cardiac dysfunction. Am J Physiol Heart Circ Physiol 304(8):H1147-58 |
| abstractText | The alpha2-isoform of the Na,K-ATPase (alpha2) is the minor isoform of the Na,K-ATPase expressed in the cardiovascular system and is thought to play a critical role in the regulation of cardiovascular hemodynamics. However, the organ system/cell type expressing alpha2 that is required for this regulation has not been fully defined. The present study uses a heart-specific knockout of alpha2 to further define the tissue-specific role of alpha2 in the regulation of cardiovascular hemodynamics. To accomplish this, we developed a mouse model using the Cre/loxP system to generate a tissue-specific knockout of alpha2 in the heart using beta-myosin heavy chain Cre. We have achieved a 90% knockout of alpha2 expression in the heart of the knockout mice. Interestingly, the heart-specific knockout mice exhibit normal basal cardiac function and systolic blood pressure, and in addition, these mice develop ACTH-induced hypertension in response to ACTH treatment similar to control mice. Surprisingly, the heart-specific knockout mice display delayed onset of cardiac dysfunction compared with control mice in response to pressure overload induced by transverse aortic constriction; however, the heart-specific knockout mice deteriorated to control levels by 9 wk post-transverse aortic constriction. These results suggest that heart expression of alpha2 does not play a role in the regulation of basal cardiovascular function or blood pressure; however, heart expression of alpha2 plays a role in the hypertrophic response to pressure overload. This study further emphasizes that the tissue localization of alpha2 determines its unique roles in the regulation of cardiovascular function. |
