Both Marfan syndrome and bicuspid aortic valve aortas exhibited immature vascular smooth muscle cells and decreased fibrillin-1 expression, while Marfan syndrome aortas showed increased medial degeneration and apoptosis similar to dilated tricuspid aortas.
Observational (n=67)
Single-blind
Yes
The histopathological similarities and differences between BAV, MFS, and TAV aortas suggest distinct mechanisms of apoptosis and degeneration, potentially explaining why angiotensin inhibition is effective in MFS but less so in TAV and BAV.
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.
Grewal et al. (Tue,) conducted a observational in Aortic dilation in Bicuspid Aortic Valve and Marfan Syndrome (n=67). Histopathological evaluation vs. TAV and BAV was evaluated on Histopathological features including fibrillin-1 expression, VSMC maturation, and apoptosis. Both Marfan syndrome and bicuspid aortic valve aortas exhibited immature vascular smooth muscle cells and decreased fibrillin-1 expression, while Marfan syndrome aortas showed increased medial degeneration and apoptosis similar to dilated tricuspid aortas.