Forkhead Box Protein 01 (Fox01) Is Key Transcription Factor Regulating Abnormal Heart Growth; Fox01 Binds Widely Throughout Genome in Mouse Model of Cardiac Hypertrophy, Activating Broad Array of Genes in Heart Cells & Stimulating Growth Signaling

The human heart is like a sponge, able to expand and grow, increasing its capacity to take up blood. In theory, an enlarged heart can also squeeze out more blood, with more power, than an average-sized heart. But in reality, for most people, this growth--known as cardiac hypertrophy--is abnormal and signals trouble. Cardiac hypertrophy is brought on by various factors, high blood pressure in particular. Existing treatments only delay the inevitable--that the spongy heart muscle becomes thicker and stiffer over time, culminating in heart failure, in which the heart can no longer contract strongly enough to pump blood through the body. A greater understanding of the molecular mechanisms driving abnormal heart growth promises to turn this around, however, and in new work, researchers at the Lewis Katz School of Medicine at Temple University (LKSOM) cast fresh light on a key molecular regulator in the heart known as FoxO1 (forkhead bozx protein 01). In an article published online on July 9, 2020 in Circulation, the Temple scientists are the first to show that the transcription factor FoxO1 attaches to and activates a wide array of genes in heart cells, leading to widespread increases in growth signaling, specifically within the heart. The article is titled “Genomic Binding Patterns of Forkhead Box Protein O1 Reveal Its Unique Role in Cardiac Hypertrophy.” "FoxO1 is a major transcription factor that regulates genes involved in metabolism and growth," said Jessica Pfleger (photo), PhD, Instructor in the Center for Translational Medicine at LKSOM and lead author of the new study.
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