Despite advances in understanding the biology of myocardial hypertrophy (enlargement of heart cells) and congestive heart failure, finding therapeutics aimed at preventing these conditions has been difficult. Cell-based methods do not capture the complexity of the intact cardiovascular system.
Using zebrafish embryos, Jason Becker, assistant professor of medicine, and colleagues have established a screening tool to identify chemical and genetic regulators of heart failure. Their system takes advantage of a cardiac natriuretic peptide gene – part of a signaling pathway that is “turned on” in myocardial hypertrophy and congestive heart failure in humans.
The researchers demonstrated that the gene, linked to a bioluminescent marker, responds to heart failure-associated pathological stimuli (both pharmacologic and genetic). In a screen of selected chemicals, they showed that two agents could block the response to a genetic stimulus that causes myocardial hypertrophy.
The screening tool, described in the March 1 issue of Cardiovascular Research, offers a unique approach for discovering potential therapeutics for myocardial hypertrophy and heart failure.
This research was supported by the National Heart, Lung and Blood Institute of the National Institutes of Health and by the Vanderbilt Physician Scientist Development Program.
