Managing myocardial infarction – and the resulting heart failure – remains a clinical challenge. To search for chemicals that can stimulate cardiac muscle cell production, Vanderbilt Institute of Chemical Biology investigators led by Tao Zhong, Ph.D., Terri Ni, Ph.D., and Eric Rellinger, M.D., turned to a novel drug discovery tool: zebrafish.
The researchers visually screened a library of chemical compounds for effects on heart size in developing zebrafish embryos using fluorescence microscopy. They report in the journal Chemistry & Biology the identification of three related compounds named Cardionogen-1, -2 and -3 that selectively enlarged embryonic hearts by expanding the number of cardiac progenitor cells. They showed that these compounds promote the differentiation of mouse embryonic stem cells into cardiac muscle cells and that they inhibit the Wnt signaling pathway in mouse cells and zebrafish embryos.
The findings demonstrate the value of an in vivo zebrafish screen for revealing compounds that stimulate cardiac muscle cell production and may lead to novel therapeutic approaches for cardiac regeneration and repair.
This research was supported by the National Institute of Neurological Disorders and Stroke, the National Heart, Lung and Blood Institute, and the National Center for Research Resources.