This article provides an overview, highlighting recent findings, of a major mechanism of gene regulation and its relevance to the pathophysiology of heart failure.
The syndrome of heart failure is a complex and highly prevalent condition, one in which the heart undergoes substantial structural remodeling. Triggered by a wide range of disease-related cues, heart failure pathophysiology is governed by both genetic and epigenetic events. Epigenetic mechanisms, such as chromatin/DNA modifications and noncoding RNAs, have emerged as molecular transducers of environmental stimuli to control gene expression. Here, we emphasize metabolic milieu, aging, and hemodynamic stress as they impact the epigenetic landscape of the myocardium.
Recent studies in multiple fields, including cancer, stem cells, development, and cardiovascular biology, have uncovered biochemical ties linking epigenetic machinery and cellular energetics and mitochondrial function. Elucidation of these connections will afford molecular insights into long-established epidemiological observations. With time, exploitation of the epigenetic machinery therapeutically may emerge with clinical relevance.
aDepartments of Internal Medicine (Cardiology)
bMolecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Correspondence to Joseph A. Hill, MD, PhD, Division of Cardiology, University of Texas Southwestern Medical Center NB11.200 6000 Harry Hines Boulevard, Dallas, TX 75390-8573, USA. E-mail: firstname.lastname@example.org