Removing vessel constriction on the embryonic heart results in changes in valve gene expression, morphology, and hemodynamics

Background: The formation of healthy heart valves throughout embryonic development is dependent on both genetic and epigenetic factors. Hemodynamic stimuli are important epigenetic regulators of valvulogenesis, but the resultant molecular pathways that control valve development are poorly understood. Here we describe how the heart and valves recover from the removal of a partial constriction (banding) of the OFT/ventricle junction (OVJ) that temporarily alters blood flow velocity through the embryonic chicken heart (HH stage 16/17). Recovery is described in terms of 24- and 48-hr gene expression, morphology, and OVJ hemodynamics. Results: Collectively, these studies show that after 24hr of recovery, important epithelial-mesenchymal transformation (EMT) genes TGF ss RIII and Cadherin 11 (CDH11) transcript levels normalize return to control levels, in contrast to Periostin and TGF ss,3 which remain altered. In addition, after 48hr of recovery, TGF ss 3 and CDH11 transcript levels remain normalized, whereas TGF ss RIII and Periostin are down-regulated. Analyses of OFT cushion volumes in the hearts show significant changes, as does the ratio of cushion to cell volume at 24hr post band removal (PBR). Morphologically, the hearts show visible alteration following band removal when compared to their control age-matched counterparts. Conclusions: Although some aspects of the genetic/cellular profiles affected by altered hemodynamics seem to be reversed, not all gene expression and cardiac growth normalize following 48hr of band removal. Developmental Dynamics 247:531-541, 2018. (c) 2017 Wiley Periodicals, Inc.