AUTHOR=Grewal Nimrat , Dolmaci Onur , Jansen Evert , Klautz Robert , Driessen Antoine , Poelmann Robert E. 

TITLE=Thoracic aortopathy in Marfan syndrome overlaps with mechanisms seen in bicuspid aortic valve disease

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1018167

DOI=10.3389/fcvm.2023.1018167

ISSN=2297-055X

ABSTRACT=<sec><title>Background</title><p>Thoracic aortopathy is a serious complication which is more often seen in patients with Marfan syndrome (MFS) and patients with a bicuspid aortic valve (BAV) than in individuals with a tricuspid aortic valve (TAV). The identification of common pathological mechanisms leading to aortic complications in non-syndromic and syndromic diseases would significantly improve the field of personalized medicine.</p></sec><sec><title>Objective</title><p>This study sought to compare thoracic aortopathy between MFS, BAV, and TAV individuals.</p></sec><sec><title>Materials and methods</title><p>Bicuspid aortic valve (BAV; <italic>n</italic> = 36), TAV (<italic>n</italic> = 23), and MFS (<italic>n</italic> = 8) patients were included. Ascending aortic wall specimen were studied for general histologic features, apoptosis, markers of cardiovascular ageing, expression of synthetic and contractile vascular smooth muscle cells (VSMC), and fibrillin-1 expression.</p></sec><sec><title>Results</title><p>The MFS group showed many similarities with the dilated BAV. Both patient groups showed a thinner intima (<italic>p</italic> &lt; 0.0005), a lower expression of contractile VSMCs (<italic>p</italic> &lt; 0.05), more elastic fiber thinning (<italic>p</italic> &lt; 0.001), lack of inflammation (<italic>p</italic> &lt; 0.001), and a decreased progerin expression (<italic>p</italic> &lt; 0.05) as compared to the TAV. Other features of cardiovascular ageing differed between the BAV and MFS. Dilated BAV patients demonstrated less medial degeneration (<italic>p</italic> &lt; 0.0001), VSMC nuclei loss (<italic>p</italic> &lt; 0.0001), apoptosis of the vessel wall (<italic>p</italic> &lt; 0.03), and elastic fiber fragmentation and disorganization (<italic>p</italic> &lt; 0.001), as compared to the MFS and dilated TAV.</p></sec><sec><title>Conclusion</title><p>This study showed important similarities in the pathogenesis of thoracic aortic aneurysms in BAV and MFS. These common mechanisms can be further investigated to personalize treatment strategies in non-syndromic and syndromic conditions.</p></sec>