June 26, 2008 New data, generated by David Ornitz and colleagues, at Washington University School of Medicine, St. Louis, have indicated a crucial role for signaling pathways that involve the protein sonic hedgehog in maintaining the blood vessels that supply the mouse heart and keep it beating.
These data have implications for drug development as they suggest that antagonists of hedgehog signaling pathways, such as those being developed as anticancer therapeutics, might have unwanted side effects.
In the study, mice lacking the ability to mediate hedgehog signaling in cells that form part of the blood vessels that supply the heart were found to die of heart failure. This was because in the absence of hedgehog signaling the blood vessels of the heart were lost, meaning that the heart cells were no longer supplied with enough oxygen and died.
Although these data indicate a need for caution when developing clinical antagonists of hedgehog signaling, it is possible that the degree of inhibition needed to have a clinical effect on tumor development might not have the effect on blood vessels of the heart that completely eliminating expression of the protein does.
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- Lavine et al. Hedgehog signaling is critical for maintenance of the adult coronary vasculature in mice. Journal of Clinical Investigation, 2008; DOI: 10.1172/JCI34561
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