| First Author | Pedram A | Year | 2016 |
| Journal | Mol Cell Endocrinol | Volume | 434 |
| Pages | 57-68 | PubMed ID | 27321970 |
| Mgi Jnum | J:248727 | Mgi Id | MGI:6095585 |
| Doi | 10.1016/j.mce.2016.06.018 | Citation | Pedram A, et al. (2016) Estrogen receptor beta signals to inhibition of cardiac fibrosis. Mol Cell Endocrinol 434:57-68 |
| abstractText | Cardiac fibrosis evolves from the cardiac hypertrophic state. In this respect, estrogen and estrogen receptor beta (ERbeta) inhibit the effects of cardiac hypertrophic peptides that also stimulate fibrosis. Here we determine details of the anti-fibrotic functions of ERbeta. In acutely isolated rat cardiac fibroblasts. E2 or a specific ERbeta agonist (betaLGND2) blocked angiotensin II (AngII) signaling to fibrosis. This resulted from ERbeta activating protein kinase A and AMP kinase, inhibiting both AngII de-phosphorylation of RhoA and the resulting stimulation of Rho kinase. Inhibition of Rho kinase from ERbeta signaling resulted in marked decrease of TGFbeta expression, connective tissue growth factor production and function, matrix metalloproteinases 2 and 9 expression and activity, and the conversion of fibroblasts to myofibroblasts. Production of collagens I and III were also significantly decreased. Several important aspects were corroborated in-vivo from betaLGND2-treated mice that underwent AngII-induced cardiac hypertrophy. Thus, ERbeta in cardiac fibroblasts prevents key aspects of cardiac fibrosis development. |
