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

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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 α1 and α2 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. Anat Rec Part A 275A:1109–1116, 2003.