Circulating Matrix Metalloproteinases for Prediction of Aortic Dilatation in Children with Bicuspid Aortic Valve: A Single-Center, Observational Study

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Oct 16

PMID 39408865

Authors

Amalia Fagarasan

Maria Oana Sasaran

Liliana Gozar

Daniela Toma

Carmen Suteu

Simina Ghiragosian-Rusu

Flavia Cristina Al-Akel

Boglarka Szabo

Adina Hutanu

Affiliations

Soon will be listed here.

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.

Citing Articles

Speckle Strain Analysis of Left Ventricular Dysfunction in Paediatric Patients with Bicuspid Aortic Valve-A Pilot Study.

Fagarasan A, Ghiragosian-Rusu S, Ghiragosian C, Gozar L, Suteu C, Toma D Children (Basel). 2025; 11(12.

PMID: 39767943 PMC: 11674767. DOI: 10.3390/children11121514.

References

Wang H, Keiser J . Expression of membrane-type matrix metalloproteinase in rabbit neointimal tissue and its correlation with matrix-metalloproteinase-2 activation. J Vasc Res. 1998; 35(1):45-54. DOI: 10.1159/000025564. View

Pasta S, Agnese V, Gallo A, Cosentino F, Di Giuseppe M, Gentile G . Shear Stress and Aortic Strain Associations With Biomarkers of Ascending Thoracic Aortic Aneurysm. Ann Thorac Surg. 2020; 110(5):1595-1604. DOI: 10.1016/j.athoracsur.2020.03.017. View

Roman M, Pugh N, Devereux R, Eagle K, Holmes K, LeMaire S . Aortic Dilatation Associated With Bicuspid Aortic Valve: Relation to Sex, Hemodynamics, and Valve Morphology (the National Heart Lung and Blood Institute-Sponsored National Registry of Genetically Triggered Thoracic Aortic Aneurysms and.... Am J Cardiol. 2017; 120(7):1171-1175. PMC: 5593782. DOI: 10.1016/j.amjcard.2017.06.061. View

Soto-Navarrete M, Pozo-Vilumbrales B, Lopez-Unzu M, Rueda-Martinez C, Fernandez M, Carmen Duran A . Experimental evidence of the genetic hypothesis on the etiology of bicuspid aortic valve aortopathy in the hamster model. Front Cardiovasc Med. 2022; 9:928362. PMC: 9393263. DOI: 10.3389/fcvm.2022.928362. View

Itoh Y . Membrane-type matrix metalloproteinases: Their functions and regulations. Matrix Biol. 2015; 44-46:207-23. DOI: 10.1016/j.matbio.2015.03.004. View

Braverman A . Bicuspid aortic valve and associated aortic wall abnormalities. Curr Opin Cardiol. 1996; 11(5):501-3. DOI: 10.1097/00001573-199609000-00009. View

Gross J, Lapiere C . Collagenolytic activity in amphibian tissues: a tissue culture assay. Proc Natl Acad Sci U S A. 1962; 48:1014-22. PMC: 220898. DOI: 10.1073/pnas.48.6.1014. View

de Almeida L, Thode H, Eslambolchi Y, Chopra S, Young D, Gill S . Matrix Metalloproteinases: From Molecular Mechanisms to Physiology, Pathophysiology, and Pharmacology. Pharmacol Rev. 2022; 74(3):712-768. DOI: 10.1124/pharmrev.121.000349. View

Cantinotti M, Giordano R, Scalese M, Murzi B, Assanta N, Spadoni I . Nomograms for two-dimensional echocardiography derived valvular and arterial dimensions in Caucasian children. J Cardiol. 2016; 69(1):208-215. DOI: 10.1016/j.jjcc.2016.03.010. View

10.

Hanedan Onan S, Baykan A, Sezer S, Narin F, Mavili E, Baykan Z . Evaluation of Cardiovascular Changes in Children with BAVs. Pediatr Cardiol. 2015; 37(3):472-81. DOI: 10.1007/s00246-015-1302-6. View

11.

Grewal N, Gittenberger-de Groot A, Poelmann R, Klautz R, Lindeman J, Goumans M . Ascending aorta dilation in association with bicuspid aortic valve: a maturation defect of the aortic wall. J Thorac Cardiovasc Surg. 2014; 148(4):1583-90. DOI: 10.1016/j.jtcvs.2014.01.027. View

12.

Hackmann A, Rubin B, Sanchez L, Geraghty P, Thompson R, Curci J . A randomized, placebo-controlled trial of doxycycline after endoluminal aneurysm repair. J Vasc Surg. 2008; 48(3):519-26. PMC: 2564857. DOI: 10.1016/j.jvs.2008.03.064. View

13.

Padang R, Bannon P, Jeremy R, Richmond D, Semsarian C, Vallely M . The genetic and molecular basis of bicuspid aortic valve associated thoracic aortopathy: a link to phenotype heterogeneity. Ann Cardiothorac Surg. 2013; 2(1):83-91. PMC: 3741809. DOI: 10.3978/j.issn.2225-319X.2012.11.17. View

14.

Fagarasan A, Sasaran M . The Predictive Role of Plasma Biomarkers in the Evolution of Aortopathies Associated with Congenital Heart Malformations. Int J Mol Sci. 2022; 23(9). PMC: 9102091. DOI: 10.3390/ijms23094993. View

15.

DeCoux A, Lindsey M, Villarreal F, Garcia R, Schulz R . Myocardial matrix metalloproteinase-2: inside out and upside down. J Mol Cell Cardiol. 2014; 77:64-72. PMC: 4312173. DOI: 10.1016/j.yjmcc.2014.09.016. View

16.

Nagase H, Visse R, Murphy G . Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res. 2006; 69(3):562-73. DOI: 10.1016/j.cardiores.2005.12.002. View

17.

Doshi A, Chikkabyrappa S . Coarctation of Aorta in Children. Cureus. 2019; 10(12):e3690. PMC: 6368362. DOI: 10.7759/cureus.3690. View

18.

Della Corte A, Quarto C, Bancone C, Castaldo C, Di Meglio F, Nurzynska D . Spatiotemporal patterns of smooth muscle cell changes in ascending aortic dilatation with bicuspid and tricuspid aortic valve stenosis: focus on cell-matrix signaling. J Thorac Cardiovasc Surg. 2008; 135(1):8-18, 18.e1-2. DOI: 10.1016/j.jtcvs.2007.09.009. View

19.

Grewal N, Klautz R, Poelmann R . Intrinsic histological and morphological abnormalities of the pediatric thoracic aorta in bicuspid aortic valve patients are predictive for future aortopathy. Pathol Res Pract. 2023; 248:154620. DOI: 10.1016/j.prp.2023.154620. View

20.

Bunton T, Biery N, Myers L, Gayraud B, Ramirez F, Dietz H . Phenotypic alteration of vascular smooth muscle cells precedes elastolysis in a mouse model of Marfan syndrome. Circ Res. 2001; 88(1):37-43. DOI: 10.1161/01.res.88.1.37. View