Removing vessel constriction on the embryonic heart results in changes in valve gene expression, morphology, and hemodynamics. Issue 3 (4th October 2017) - Menon, Vinal
Abstract : 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 24 hr of recovery, important epithelial‐mesenchymal transformation (EMT) genes TGFßRIII and Cadherin 11 (CDH11) transcript levels normalize return to control levels, in contrast to Periostin and TGFß, 3 which remain altered. In addition, after 48 hr of recovery, TGFß3 and CDH11 transcript levels remain normalized, whereas TGFßRIII 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 24 hr 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 48 hr of band removal. Developmental Dynamics 247:531–541, 2018 . © 2017 Wiley Periodicals, Inc. Key Findings: We have previously shown that altered hemodynamics (by OFT banding) has negative consequences at the cellular and molecular level which could affect valve development. This manuscript aims to investigate the response to restoration of hemodynamic stimuli. As shown in the report, anomalies resulting due to perturbed hemodynamics, morphologically and genetically, are not necessarily rescued even 48 h after removing the band.