| First Author | Correll RN | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 2059 |
| PubMed ID | 30765833 | Mgi Jnum | J:275536 |
| Mgi Id | MGI:6304636 | Doi | 10.1038/s41598-019-39515-5 |
| Citation | Correll RN, et al. (2019) Overlapping and differential functions of ATF6alpha versus ATF6beta in the mouse heart. Sci Rep 9(1):2059 |
| abstractText | Hemodynamic stress on the mammalian heart results in compensatory hypertrophy and activation of the unfolded protein response through activating transcription factor 6alpha (ATF6alpha) in cardiac myocytes, but the roles of ATF6alpha or the related transcription factor ATF6beta in regulating this hypertrophic response are not well-understood. Here we examined the effects of loss of ATF6alpha or ATF6beta on the cardiac response to pressure overload. Mice gene-deleted for Atf6 or Atf6b were subjected to 2 weeks of transverse aortic constriction, and each showed a significant reduction in hypertrophy with reduced expression of endoplasmic reticulum (ER) stress-associated proteins compared with controls. However, with long-term pressure overload both Atf6 and Atf6b null mice showed enhanced decompensation typified by increased heart weight, pulmonary edema and reduced function compared to control mice. Our subsequent studies using cardiac-specific transgenic mice expressing the transcriptionally active N-terminus of ATF6alpha or ATF6beta revealed that these factors control overlapping gene expression networks that include numerous ER protein chaperones and ER associated degradation components. This work reveals previously unappreciated roles for ATF6alpha and ATF6beta in regulating the pressure overload induced cardiac hypertrophic response and in controlling the expression of genes that condition the ER during hemodynamic stress. |
