Towards a BETter understanding of cardiac fibrosis

Abstract

Fibroblast activation is a hallmark feature of pathological remodeling of the heart and represents an attractive target for therapeutic intervention. Pharmacological inhibition of chromatin remodeling enzymes reduces cardiac fibrosis, but the underlying transcriptional regulatory mechanisms remain poorly understood. Using single-cell genomics to profile alterations in the transcriptional and chromatin landscape during stress-induced cardiac remodeling, Alexanian et al. discovered a critical role for Mesenchyme Homeobox 1 in the regulation of myofibroblast activation and cardiac fibrosis. We briefly review these important findings and comment on the significance of their work.

Keywords

Cardiac fibrosis / chromatin / fibroblast activation / heart failure

References

[1] Tsao CW,Almarzooq ZI.Heart disease and stroke statistics-2022 update: a report from the American heart association.Circulation2022;145:e153-639

[2] Alexanian M,Micheletti R.A transcriptional switch governs fibroblast activation in heart disease.Nature2021;595:438-43 PMCID:PMC8341289

[3] Anand P,Lin CY.BET bromodomains mediate transcriptional pause release in heart failure.Cell2013;154:569-82 PMCID:PMC4090947

[4] Spiltoir JI,Cavasin MA.BET acetyl-lysine binding proteins control pathological cardiac hypertrophy.J Mol Cell Cardiol2013;63:175-9 PMCID:PMC4089995

[5] Filippakopoulos P,Picaud S.Selective inhibition of BET bromodomains.Nature2010;468:1067-73 PMCID:PMC3010259

[6] Wei Z,Li H.Molecular mechanism of mesenchyme homeobox 1 in transforming growth factor β1-induced.P3117:59 PMCID:PMC7199492

[7] Lu D,Li J.Meox1 accelerates myocardial hypertrophic decompensation through Gata4.Cardiovasc Res2018;114:300-11

[8] Wu Y,Roscoe BP.Highly efficient therapeutic gene editing of human hematopoietic stem cells.Nat Med2019;25:776-83 PMCID:PMC6512986