Figure 5

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.