3/2/2023 0 Comments Protein scaffold of a heartIn vitro evidence suggests that the scaffold protein muscle A-kinase anchoring protein β (mAKAPβ) serves as a nodal organizer of hypertrophic signaling. Targeting of the underlying physical architecture of signaling networks, including mAKAPβ signalosome formation, may constitute an effective therapeutic strategy for the prevention and treatment of pathological remodeling and heart failure.Ībstract = "Background-Cardiac myocyte hypertrophy is regulated by an extensive intracellular signal transduction network. Conclusions-mAKAPβ orchestrates signaling that regulates pathological cardiac remodeling in mice. Furthermore, mAKAPβ knockout inhibited pathological gene expression directed by myocyteenhancer factor-2 and nuclear factor of activated T-cell transcription factors that associate with the scaffold. This improvement in cardiac status correlated with the attenuated activation of signaling pathways coordinated by the mAKAPβ scaffold, including the decreased phosphorylation of protein kinase D1 and histone deacetylase 4 that we reveal to participate in a new mAKAP signaling module. Accordingly, mAKAPβ knockout inhibited myocardial apoptosis and the development of interstitial fibrosis, left atrial hypertrophy, and pulmonary edema. In contrast to 29% of control mice (n=24), only 6% of mAKAPβ knockout mice (n=31) died in the 16 weeks of pressure overload (P=0.02). mAKAPβ targeting prevented the development of heart failure associated with long-term transverse aortic constriction, conferring a survival benefit. Methods and Results-Using conditional, cardiac myocyte-specific gene deletion, we now demonstrate that mAKAPβ expression in mice is important for the cardiac hypertrophy induced by pressure overload and catecholamine toxicity. However, the relevance of mAKAPβ signalosomes to pathological remodeling and heart failure in vivo remains unknown. Background-Cardiac myocyte hypertrophy is regulated by an extensive intracellular signal transduction network.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |