AUTHOR=Seim Bjørn Edvard , Holt Margrethe Flesvig , Ratajska Aleksandra , Michelsen Annika , Ringseth Monica Myklebust , Halvorsen Bente Evy , Skjelland Mona , Kvitting John-Peder Escobar , Lundblad Runar , Krohg-Sørensen Kirsten , Osnes Liv T. N. , Aukrust Pål , Paus Benedicte , Ueland Thor 

TITLE=Markers of extracellular matrix remodeling and systemic inflammation in patients with heritable thoracic aortic diseases

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.1073069

DOI=10.3389/fcvm.2022.1073069

ISSN=2297-055X

ABSTRACT=Abstract
Background: In approximately 20% of patients with thoracic aortic aneurysms or dissections a heritable thoracic aortic disease (HTAD) is suspected. Several monogenic connective tissue diseases imply high risk of aortic disease, including both non-syndromic and syndromic forms. There are some studies assessing inflammation and extracellular matrix remodeling (ECM) in patients with non-hereditary aortic disease, but such studies in patients with hereditary diseases are scarce.
Aims: To quantify markers of ECM and inflammation in patients with vascular connective tissue diseases versus healthy controls.
Methods: Patients with Loeys-Dietz syndrome (LDS, n=12), Marfan syndrome (MFS, n=11), and familial thoracic aortic aneurysm 6 (FTAA6, n=9), i.e. actin alpha 2 (ACTA2) pathogenic variants, were recruited. Exome or genome sequencing was performed for genetic diagnosis. Several markers of inflammation and ECM remodeling were measured in plasma by enzyme immunoassays. Flow cytometry of T cell subpopulations was performed on a subgroup of patients. For comparison, blood samples were drawn from 14 healthy controls. 
Results: (i) All groups of HTAD patients had increased levels matrix metalloproteinase-9 (MMP-9) as compared with healthy controls, also in adjusted analyses, reflecting altered ECM remodeling. (ii) LDS patients had increased levels of pentraxin-3 (PTX3), reflecting systemic inflammation. (iii) LDS patients had increased levels of soluble CD25, a marker of T cell activation. 
Conclusion: Our data suggest that that upregulated MMP-9, a matrix degrading enzyme, is a common feature of several subgroups of HTAD. In addition, LDS patients as increased levels of PTX3 reflecting systemic and in particular vascular inflammation.