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

Authors :
Grewal N
Franken R
Mulder BJ
Goumans MJ
Lindeman JH
Jongbloed MR
DeRuiter MC
Klautz RJ
Bogers AJ
Poelmann RE
Groot AC
Source :
Heart and vessels [Heart Vessels] 2016 May; Vol. 31 (5), pp. 795-806. Date of Electronic Publication: 2015 Jul 01.
Publication Year :
2016

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.

Details

Language :
English
ISSN :
1615-2573
Volume :
31
Issue :
5
Database :
MEDLINE
Journal :
Heart and vessels
Publication Type :
Academic Journal
Accession number :
26129868
Full Text :
https://doi.org/10.1007/s00380-015-0703-z