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Published on: February 23, 2020
Circulating Matrix Metalloproteinases for Prediction of Aortic Dilatation in Children with Bicuspid Aortic Valve: A
Amalia Făgărășan1,2, Maria Oana Săsăran3, Liliana Gozar1,2
1Department of Pediatrics III, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540142 Târgu Mureș, Romania.
Insights
Tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were higher in children with bicuspid aortic valve (BAV) but no aortic dilatation. TIMP-1 inversely correlated with aortic size, suggesting a potential role in BAV-associated aortic disease progression.
Area of Science:
- Cardiovascular Medicine
- Biomarkers
- Genetics
Background:
- Bicuspid aortic valve (BAV) is a common congenital heart defect associated with aortic dilatation and aneurysm formation.
- Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play a crucial role in extracellular matrix remodeling, implicated in aortic wall degradation.
- Identifying biomarkers for early detection of aortic dilatation progression in pediatric BAV patients is critical for timely intervention.
Purpose of the Study:
- To investigate the role of MMP-1, MMP-2, MMP-9, and TIMP-1 in children with BAV and their association with aortic dilatation.
- To determine if these MMPs and TIMP-1 can serve as predictors of aortic aneurysm formation in pediatric BAV patients.
Main Methods:
- A cohort of 73 children with BAV was divided into two groups: controls (n=43) and those with aortic dilatation (n=30).
- Cardiac ultrasound was performed to assess aortic dimensions.
- Serum levels of MMP-1, MMP-2, MMP-9, and TIMP-1 were quantified using xMAP technology.
Main Results:
- TIMP-1 levels were significantly higher in the BAV control group compared to the BAV with aortic dilatation group.
- TIMP-1 showed an inverse correlation with aortic annulus absolute size and z-score, and ascending aorta z-score.
- No significant correlation was found between other MMPs (MMP-1, MMP-2, MMP-9) and aortic dilatation, nor between aortic phenotype and dilatation presence.
Conclusions:
- TIMP-1 may play a protective role in the early stages of BAV-associated aortic disease, as indicated by its higher levels and inverse correlation with aortic size in patients without dilatation.
- Further longitudinal studies in pediatric populations are warranted to explore the predictive significance of MMPs and TIMP-1 screening for aortic aneurysm development in BAV individuals.
- These findings suggest potential utility of TIMP-1 as a biomarker in monitoring BAV-associated aortic remodeling.
Abstract:
Circulating biomarkers have been proposed for early identification of aortic dilatation progression associated with bicuspid aortic valve (BAV), but matrix metalloproteinases (MMPs) are distinguished as signatures of increased extracellular matrix degradation, a landmark of aneurysm formation. The current study aims to identify the role of MMP-1, MMP-2, MMP-9, and the MMP inhibitor, TIMP-1, in identifying aortic dilation in children with BAV. We conducted a study on 73 children divided into two study groups, depending on the presence of aortic dilatation (group 1-43 BAV controls and group 2-30 children with BAV and aortic dilatation). Each patient underwent a cardiac ultrasound and, in each case, serum MMP-1, MMP-2, MMP-9, and TIMP-1 were quantified using xMAP technology. Comparison of the MMPs between the two study groups revealed significantly higher values only in the case of TIMP-1, among BAV controls. Moreover, the same TIMP-1 inversely correlated with aortic annulus absolute size and z score, as well as with ascending aorta z score. No particular correlation between the aortic phenotype and the presence of aortic dilatation was found. Future longitudinal research starting at pediatric ages could show the significance of MMPs screening in BAV individuals as predictors of aortic aneurysm formation.
