Collagen type VI expression during cardiac development and in human fetuses with trisomy 21

Abstract

The role played by specific extracellular matrix molecules in normal endocardial cushion differentiation into valves and septa remains to be established. In this respect, type collagen VI is of particular interest because genes encoding the ␣1 and ␣2 chains are located on chromosome 21, and defects involving the atrioventricular (AV) cushions are frequent in trisomy 21. Collagen VI expression was studied in normal human embryonic and fetal hearts (5-18 weeks of development) and compared by immunohistochemistry with results from fetuses (10 -16 weeks of development) with trisomy 21. During normal endocardial cushion differentiation (5-8 weeks) there was marked collagen VI expression in the AV cushions, whereas only minor expression was seen in the outflow tract cushions. In the normal fetuses (10 -18 weeks), collagen VI in the AV cushions had condensed into a marked zone on the atrial side of the leaflets, as well as subendocardially in other regions of high shear stress. Morphological defects involving the endocardial cushion-derived structures were present in all trisomy 21 cases. An abnormally large membranous septum was observed in three cases. An AV septal defect (AVSD) was present in two, while one had a ventricular septal defect (VSD). Two cases presented with a secondary atrial septal defect (ASDII), and one had an AVSD. Mild to moderate valve dysmorphia was found in all cases. Collagen VI staining in trisomy 21 was more intense than in the normal subjects; however, there were no differences in the spatial expression patterns. We conclude that collagen VI is expressed in the AV cushions and persists during valve differentiation. Collagen VI is more prominent in fetal trisomy 21 hearts than in normal hearts. We hypothesise that collagen VI has a role in the development of heart defects involving endocardial cushion differentiation-specifically in the AV canal, the most common site of malformations affecting children with trisomy 21.

Accessory Atrioventricular Myocardial Connections in the Developing Human Heart

“…A detailed description of staining protocols can be found in previous publications. 11,12 All embryos, fetuses, and neonates were separated into 4 groups of successive gestational stages of development according to pregnancy duration and crown-rump-length (CRL): group 1, from 4 weeks/CRL 5 mm to 6 weeks/CRL 11 mm (nϭ2); group 2, from 6 weeks/CRL 11 mm to 10 weeks/CRL 40 mm (nϭ7); group 3, from 10 weeks/CRL 40 mm to 20 weeks/CRL 164 -170 mm (nϭ27); and group 4, from 20 weeks/CRL 164 -170 mm to birth/neonates (nϭ9).…”

Basics of Cardiac Development for the Understanding of Congenital Heart Malformations

“…The cushion material will mainly condense into what is known as the membranous part of the atrioventricular septum. We have recently shown in human trisomy 21 fetal hearts, studied for their collagen VI distribution, that the membranous septum is exceptionally large in these cases (27). Ventricular outflow tract septation.…”

“…the transforming growth factor (TGF)-␤2 knockout mouse (26). In human patients, it is often found in trisomy 21 or Down syndrome patients (27,28).…”

Epicardium‐derived cells are important for correct development of the Purkinje fibers in the avian heart

“…These epicardium-derived cells (EPDCs) can migrate into the myocardium and differentiate into interstitial, subendocardial, and coronary adventitial fibroblasts, as well as coronary smooth muscle cells Vrancken Peeters et al, 1999). Several studies have demonstrated crucial roles of EPDCs in the formation of the compact myocardium (Kwee et al, 1995;Yang et al, 1995;Gittenberger-de Groot et al, 2000;Lie-Venema et al, 2003) and coronary development , while a morphogenic role for EPDCs in valve development has also been postulated , 2003a.…”