Pathogenesis of aortic wall complications in Marfan syndrome.

Background: Patients with Marfan (MFS) syndrome and patients with a bicuspid aortic valve (BAV) are more prone to develop aortic dilation and dissection compared to persons with a tricuspid aortic valve (TAV). To elucidate potential common as well as distinct pathways of clinical relevance, we compared the histopathological substrates of aortic pathology.

Patient And Methods: Ascending aortic wall specimen were divided in five groups: BAV (n=36) and TAV (n=23) without and with dilation and non-dilated MFS (n=8). We performed routine histology to study aortic wall features based on the aortic consensus statement. Immunohistological markers for vascular smooth muscle cell (VSMC) maturation, and expression of fibrillin-1 were additionally investigated for the underlying pathogenesis.

Results: On basis of the routine histology the aorta in MFS was similar to the aorta in dilated TAVs (overall medial degeneration, elastic fiber fragmentation, loss and disorganization, , and VSMC nuclei loss). The other markers aided in clustering the MFS and BAV patients with a significantly lower fibrillin-1 expression as compared to the TAVs (p<0.05), a lower level of differentiated VSMC markers (p<0.05) and elastic fiber thinning.

Conclusions: Pathogenesis of aortopathy in MFS overlaps with mechanisms seen in BAV and TAV, leading to a so called double hit hypothesis for aortic complications in MFS. The ascending aortic wall in MFS is immature with undifferentiated VSMCs and low levels of fibrillin-1. The immature media becomes even more vulnerable for aortopathy due to other degenerative features which develop probably as a direct consequence of the fibrillin-1 mutation.