In This Issue

摘要

The?most?commonly?diagnosed?congenital?heart?defects?are?cardiac?valve?malformations.?Understand-ing?the?molecular?mechanisms?underlying?valve?development?should?provide?new?avenues?of?researchinto?the?origin?of?cardiac?valve?defects.?In?this?context,?Luna-Zurita?and?colleagues?have?determinedthat?integration?of?endocardial-Notch1?and?myocardial-Bmp2?signals?in?prevalvular?regions?of?themouse?heart?is?critical?to?embryonic?cardiac?valve?formation?(3493–3507).?In?higher?vertebrates,?heartvalve?primordia?are?generated?from?endocardial?cells?that?undergo?epithelial-to-mesenchyme?transi-tion?(EMT).?In?the?study,?Luna-Zurita?and?colleagues?show?that?during?cardiac?valve?formation,?EMTis?limited?to?prospective?valve?territories?by?the?interplay?between?endocardial-Notch1?and?myocardial-Bmp2?to?regulate?the?Snail1?transcription?factor.?Constitutive?Notch1?activity?in?endocardial?cells?initi-ated?a?partial?(noninvasive)?Snail1-driven?EMT?in?vitro?that?became?invasive?upon?Bmp2?treatment.In?addition,?ectopic?myocardial?Notch1?expression?and?loss-of-function?experiments?indicated?thatNotch1?represses?Bmp2?in?cardiac?cells?while?Bmp2?inactivationin?the?myocardium?impaired?Notch1?activity.?This?embryonicNotch1/Bmp2/Snail1?relationship?may?also?be?relevant?in?adultvalve?disease?or?atherosclerosis,?as?these?diseases?share?featuressuch?as?tissue?inflammation,?EMT,?fibrosis,?and?calcification.