| First Author | Imaeda A | Year | 2019 |
| Journal | Biochem Biophys Res Commun | Volume | 510 |
| Issue | 1 | Pages | 149-155 |
| PubMed ID | 30683314 | Mgi Jnum | J:291225 |
| Mgi Id | MGI:6443381 | Doi | 10.1016/j.bbrc.2019.01.070 |
| Citation | Imaeda A, et al. (2019) Myofibroblast beta2 adrenergic signaling amplifies cardiac hypertrophy in mice. Biochem Biophys Res Commun 510(1):149-155 |
| abstractText | Abnormal beta-adrenergic signaling plays a central role in human heart failure. In mice, chronic beta-adrenergic receptor (betaAR) stimulation elicits cardiac hypertrophy. It has been reported that cultured cardiac fibroblasts express betaAR; however, the functional in vivo requirement of betaAR signaling in cardiac fibroblasts during the development of cardiac hypertrophy remains elusive. beta2AR null mice exhibited attenuated hypertrophic responses to chronic betaAR stimulation upon continuous infusion of an agonist, isoprenaline (ISO), compared to those in wildtype controls, suggesting that beta2AR activation in the heart induces pro-hypertrophic effects in mice. Since beta2AR signaling is protective in cardiomyocytes, we focused on beta2AR signaling in cardiac myofibroblasts. To determine whether beta2AR signaling in myofibroblasts affects cardiac hypertrophy, we generated myofibroblast-specific transgenic mice (TG) with the catalytic subunit of protein kinase A (PKAcalpha) using Cre-loxP system. Myofibroblast-specific PKAcalpha overexpression resulted in enhanced heart weight normalized to body weight ratio, associated with an enlargement of cardiomyocytes at 12 weeks of age, indicating that myofibroblast-specific activation of PKA mediates cardiac hypertrophy in mice. Neonatal rat cardiomyocytes stimulated with conditioned media from TG cardiac fibroblasts likewise exhibited significantly more growth than those from controls. Thus, beta2AR signaling in myofibroblasts plays a substantial role in ISO-induced cardiac hypertrophy, possibly due to a paracrine effect. beta2AR signaling in cardiac myofibroblasts may represent a promising target for development of novel therapies for cardiac hypertrophy. |
