Obesity is a major cause of heart disease and heart failure. Five-year death rates following first hospital admission for heart failure is greater than 40%, stressing the need for new therapeutic strategies. Prolonged heart enlargement and heart stiffness plays a critical role in the development of heart failure, yet little is known about how changes in individual cells reading their genes and the link between obesity and changes in heart structure and function.
Every cell within the body has a blueprint (DNA) to express tens of thousands of different genes yet in any given cell type only a small subset of these genes are expressed. The selective expression of these genes is what gives rise to cell, tissue, and organ specific function. That is, a cell in the eye’s retina is different than a cell in the heart because the cells express different genes. In the same manner, the diseased heart expresses genes that it normally would not, which lead to its enlargement and stiffening.
This selective use of genes is regulated by complex mechanisms that are only beginning to be understood and involve the regulation of adding and removing chemical marks (epigenetics) to the molecular packages (chromatin) that hold the blueprints (genes).
Previous reports from the team at UNR and others have found that inhibition of a specific class of epigenetic regulators within the heart, histone deacetylases (HDAC), block heart enlargement and stiffness in animal models of heart failure, yet a role for HDAC in obesity has yet to be examined.
This project is investigating the role of HDAC as epigenetic activators of heart enlargement and stiffness, with emphasis on the function of HDAC in controlling obesity-induced heart dysfunction. In addition, this project is focusing on dietary food components that block HDAC and therefore would protect against heart enlargement and stiffness.