Histopathology of aortic complications in bicuspid aortic valve versus Marfan syndrome: relevance for therapy?

Abstract

Patients with bicuspid aortic valve (BAV) and patients with Marfan syndrome (MFS) are more prone to develop aortic dilation and dissection compared to persons with a tricuspid aortic valve (TAV). To elucidate potential common and distinct pathways of clinical relevance, we compared the histopathological substrates of aortopathy. Ascending aortic wall biopsies were divided in five groups: BAV (n = 36) and TAV (n = 23) without and with dilation and non-dilated MFS (n = 8). General histologic features, apoptosis, the expression of markers for vascular smooth muscle cell (VSMC) maturation, markers predictive for ascending aortic dilation in BAV, and expression of fibrillin-1 were investigated. Both MFS and BAV showed an altered distribution and decreased fibrillin-1 expression in the aorta and a significantly lower level of differentiated VSMC markers. Interestingly, markers predictive for aortic dilation in BAV were not expressed in the MFS aorta. The aorta in MFS was similar to the aorta in dilated TAV with regard to the presence of medial degeneration and apoptosis, while other markers for degeneration and aging like inflammation and progerin expression were low in MFS, comparable to BAV. Both MFS and BAV aortas have immature VSMCs, while MFS and TAV patients have a similar increased rate of medial degeneration. However, the mechanism leading to apoptosis is expected to be different, being fibrillin-1 mutation induced increased angiotensin-receptor-pathway signaling in MFS and cardiovascular aging and increased progerin in TAV. Our findings could explain why angiotensin inhibition is successful in MFS and less effective in TAV and BAV patients.

Marfan Syndrome Versus Bicuspid Aortic Valve Disease: Comparative Analysis of Obstetric Outcome and Pregnancy-Associated Immediate and Long-Term Aortic Complications

“…Diameters of the ascending segment of the aorta were larger in ever-pregnant women with bicuspid aortic valve disease than with Marfan syndrome, whereas more distal segments of the aorta were more dilated in ever-pregnant women with Marfan syndrome than with bicuspid aortic valve disease. Previous investigations confirmed that the anatomic site of major aortic pathology was distinct in both entities and showed that the maximal aortic dilatation occurred at the ascending aorta in individuals with bicuspid aortic valve disease [37,38]. In accordance with the literature, we found coarctation of the aorta only with bicuspid aortic valve disease but not with Marfan syndrome [39], and identified mitral valve prolapse only with Marfan syndrome but not with bicuspid aortic valve disease [40].…”

Biomechanical properties of the thoracic aorta in Marfan patients

“…Additionally, Pham et al found BAV patients, which have been structurally and mechanically linked to MFS patients (13,14,23), to have significantly more isotropic aortic tissue than other AsAA patients, as also found in MFS patients in the current study (24). Pham also found a trend of age-related thickening in BAV tissue, agreeing with our MFS findings.…”

Year in review

“…Phillippi with Gleason and Vorp at University of Pittsburgh further characterized the medial matrix remodeling of the BAV aorta and found unique patterns as compared to TAV patients(74). Grewal and co-workers compared the histopathology of BAV, TAV, and Marfan aortic tissue and found both similarities and differences between all three groups with respect to parameters of matrix remodeling and vascular smooth muscle markers(75). The complexity of the histopathology remains high and it is not clear what molecular pathways are unique to the BAV aorta.…”