Postnatal Ablation of Foxm1 from Cardiomyocytes Causes Late Onset Cardiac Hypertrophy and Fibrosis without Exacerbating Pressure Overload-Induced Cardiac Remodeling

摘要: Heart disease remains a leading cause of morbidity and mortality in the industrialized world. Hypertrophic cardiomyopathy is most common genetic cardiovascular disorder sudden cardiac death. Foxm1 transcription factor (also known as HFH-11B, Trident, Win or MPP2) plays an important role pathogenesis various cancers critical mediator post-injury repair multiple organs. has been previously shown to be essential for heart development proliferation embryonic cardiomyocytes. However, postnatal injury not evaluated. To delete cardiomyocytes, αMHC-Cre/Foxm1(fl/fl) mice were generated. Surprisingly, exhibited normal cardiomyocyte at day seven had no defects structure function but developed hypertrophy fibrosis late life. The aged Foxm1-deficient was associated with reduced expression Hey2, regulator homeostasis, increased genes remodeling, including MMP9, αSMA, fibronectin vimentin. We also found that following aortic constriction mRNA protein induced deletion did exacerbate chronic pressure overload. Our results demonstrate regulates age-induced fibrosis.