Kyung Chan Park, Nicholas T Crump, Niamh Louwman, Steve Krywawych, Yuen Jian Cheong, Iolanda Vendrell, Eleanor K Gill, Mala Gunadasa-Rohling, Kerrie L Ford, David Hauton, Marjorie Fournier, Elisabete Pires, Lydia Watson, Gerald Roseman, James Holder, Andreas Koschinski, Ricardo Carnicer, M Kate Curtis, Manuela Zaccolo, Alzbeta Hulikova, Roman Fischer, Holger B Kramer, James S O McCullagh, Sophie Trefely, Thomas A Milne, Pawel Swietach
Propiogenic substrates and gut bacteria produce propionate, a post-translational protein modifier. In this study, we used a mouse model of propionic acidaemia (PA) to study how disturbances to propionate metabolism result in histone modifications and changes to gene expression that affect cardiac function. Plasma propionate surrogates were raised in PA mice, but female hearts manifested more profound changes in acyl-CoAs, histone propionylation and acetylation, and transcription. These resulted in moderate diastolic dysfunction with raised diastolic Ca2+ , expanded end-systolic ventricular volume and reduced stroke volume...
December 2023: Nat Cardiovasc Res