Endocardial Fibroelastosis is Secondary to Hemodynamic Alterations in the Chick Embryonic Model of Hypoplastic Left Heart Syndrome.

BACKGROUND: Endocardial fibroelastosis (EFE) is a diffuse thickening of the ventricular endocardium, causing myocardial dysfunction and presenting as unexplained heart failure in infants and children. One of the postulated causes is persistent and increased wall tension in the ventricles. RESULTS: To examine whether reduced ventricular pressure in a chick model of hypoplastic left heart syndrome (HLHS) induced by left atrial ligation (LAL) at embryonic day (ED) 4 is associated with EFE at later stages, myocardial fibrosis was evaluated by histology and immunoconfocal microscopy and mass spectrometry (MS) at ED12. Immunohistochemistry with collagen I antibody clearly showed a significant thickening of the layer of subendocardial fibrous tissue in LAL hearts, and MS proved this significant increase of collagen I. To provide further insight into pathogenesis of this increased fibroproduction, hypoxyprobe staining revealed an increased extent of hypoxic regions, normally limited to the interventricular septum, in the ventricular myocardium of LAL hearts at ED8. CONCLUSIONS: Abnormal hemodynamic loading during heart development leads to myocardial hypoxia, stimulating collagen production in the subendocardium. Therefore, EFE in this chick embryonic model of HLHS appears to be a secondary effect of abnormal hemodynamics. Developmental Dynamics 247:509-520, 2018. © 2017 Wiley Periodicals, Inc.

Analysis of dermal fibroblasts isolated from neonatal and child cleft lip and adult skin: Developmental implications on reconstructive surgery.

The nonsyndromic cleft is one of the most frequent congenital defects in humans. Clinical data demonstrated improved and almost scarless neonatal healing of reparative surgery. Based on our previous results on crosstalk between neonatal fibroblasts and adult keratinocytes, the present study focused on characterization of fibroblasts prepared from cleft lip tissue samples of neonates and older children, and compared them with samples isolated from normal adult skin (face and breast) and scars. Although subtle variances in expression profiles of children and neonates were observed, the two groups differed significantly from adult cells. Compared with adult cells, differences were observed in nestin and smooth muscle actin (SMA) expression at the protein and transcript level. Furthermore, fibroblast to myofibroblast differentiation drives effective wound healing and is largely regulated by the cytokine, transforming growth factor-ß1 (TGF-ß1). Dysregulation of the TGF-ß signalling pathway, including low expression of the TGF-ß receptor II, may contribute to reducing scarring in neonates. Fibroblasts of facial origin also exhibited age independent differences from the cells prepared from the breast, reflecting the origin of the facial cells from neural crest-based ectomesenchyme.