| First Author | Xiong X | Year | 2022 |
| Journal | Biochem Biophys Res Commun | Volume | 625 |
| Pages | 31-37 | PubMed ID | 35944361 |
| Mgi Jnum | J:330806 | Mgi Id | MGI:7332526 |
| Doi | 10.1016/j.bbrc.2022.07.106 | Citation | Xiong X, et al. (2022) alphaSMA-Cre-mediated Ogt deletion leads to heart failure and vascular smooth muscle cell dysfunction in mice. Biochem Biophys Res Commun 625:31-37 |
| abstractText | Dilated cardiomyopathy, a type of heart muscle disease defined by the presence of left ventricular dilatation and contractile dysfunction, is an important cause of sudden cardiac death and heart failure. O-GlcNAcylation is an important post-translational modification of proteins by the addition of O-GlcNAc moieties at serine or threonine residues. Several studies have shown that proper control of O-GlcNAcylation is required for maintaining physiological function of heart by using Ogt (O-GlcNAc transferase) cardiomyocyte-specific knockout mouse models. In this study, we generated a new mouse model (alphaSMA-Ogt KO) in which Ogt was deleted in both cardiomyocytes and smooth muscle cells by crossing Ogt floxed mice with alphaSMA-Cre mice. alphaSMA-Cre-mediated Ogt deletion in mice led to severe postnatal lethality; the survived mice were smaller than control mice, had dilated hearts, and showed observable signs of heart failure. Moreover, the alphaSMA-Ogt KO heart had more apoptotic cells and fibrosis. The arteries of alphaSMA-Ogt KO mice exhibited significantly reduced expression of contractile genes and a trend towards arterial stiffness. In conclusion, our data emphasize the importance of OGT in maintaining normal heart function and reveal a novel role of OGT in regulating arterial contractility. |
