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. 2019 Nov 5;9:16059. doi: 10.1038/s41598-019-52558-y

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Sensing of immature intracardiac flow patterns activates a Notch mediated regenerative program, recapitulating cardiac valve development. At embryonic developmental stages a feedback loop where intracardiac flow dynamics regulate klf2a and notch1b results in the restricted expression of notch1b at the high sheer-stress areas of the heart: the atrioventricular valve and the outflow tract. The intracardiac flow pattern following valvular damage, is disturbed causing an increase in the retrograde blood flow fraction, reminiscent of the flow pattern of earlier stage of embryogenesis. As a result, notch1b is re-activated ectopically the ventricular endocardium. When cardiac valves regenerate and flow dynamics are restored, notch1b expression gets restricted at the atrioventricular canal and the outflow tract.