The Predictive Role of Plasma Biomarkers in the Evolution of Aortopathies Associated with Congenital Heart Malformations

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 May 14

PMID 35563383

Authors

Amalia Fagarasan

Maria Oana Sasaran

Affiliations

Soon will be listed here.

Abstract

Dilatation of the aorta is a constantly evolving condition that can lead to the ultimate life-threatening event, acute aortic dissection. Recent research has tried to identify quantifiable biomarkers, with both diagnostic and prognostic roles in different aortopathies. Most studies have focused on the bicuspid aortic valve, the most frequent congenital heart disease (CHD), and majorly evolved around matrix metalloproteinases (MMPs). Other candidate biomarkers, such as asymmetric dimethylarginine, soluble receptor for advanced glycation end-products or transforming growth factor beta have also gained a lot of attention recently. Most of the aortic anomalies and dilatation-related studies have reported expression variation of tissular biomarkers. The ultimate goal remains, though, the identification of biomarkers among the serum plasma, with the upregulation of circulating MMP-1, MMP-2, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), asymmetric dimethylarginine (ADMA), soluble receptor for advanced glycation end-products (sRAGE) and transforming growth factor beta (TGF-β) being reported in association to several aortopathies and related complications in recent research. These molecules are apparently quantifiable from the early ages and have been linked to several CHDs and hereditary aortopathies. Pediatric data on the matter is still limited, and further studies are warranted to elucidate the role of plasmatic biomarkers in the long term follow-up of potentially evolving congenital aortopathies.

Citing Articles

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

Fagarasan A, Sasaran M, Gozar L, Toma D, Suteu C, Ghiragosian-Rusu S Int J Mol Sci. 2024; 25(19).

PMID: 39408865 PMC: 11476682. DOI: 10.3390/ijms251910538.

The Importance of Aortic Valve Bicuspid Phenotype in Valvular Evolution in Pediatric Patients: A Case Report and Literature Mini-Review.

Fagarasan A, Gurzu S, Satala C, Hagau A Int J Mol Sci. 2023; 24(18).

PMID: 37762329 PMC: 10531046. DOI: 10.3390/ijms241814027.

The Role of Galectin-3 in Predicting Congenital Heart Disease Outcome: A Review of the Literature.

Fagarasan A, Sasaran M, Gozar L, Crauciuc A, Banescu C Int J Mol Sci. 2023; 24(13).

PMID: 37445687 PMC: 10342020. DOI: 10.3390/ijms241310511.

References

Chen H, Wang D . Nitric oxide inhibits matrix metalloproteinase-2 expression via the induction of activating transcription factor 3 in endothelial cells. Mol Pharmacol. 2004; 65(5):1130-40. DOI: 10.1124/mol.65.5.1130. View

Simpson J, Pushparajah K . Dilatation of the Aorta in Bicuspid Aortic Valve Disease. Circ Cardiovasc Imaging. 2020; 13(3):e010448. DOI: 10.1161/CIRCIMAGING.120.010448. View

Tan J, Gatzoulis M, Ho S . Aortic root disease in tetralogy of Fallot. Curr Opin Cardiol. 2006; 21(6):569-72. DOI: 10.1097/01.hco.0000245732.09594.2f. View

Habchi K, Ashikhmina E, Montiero Vieira V, Shahram J, Isselbacher E, Sundt 3rd T . Association between bicuspid aortic valve morphotype and regional dilatation of the aortic root and trunk. Int J Cardiovasc Imaging. 2016; 33(3):341-349. PMC: 6377809. DOI: 10.1007/s10554-016-1016-8. View

Dietz H . TGF-beta in the pathogenesis and prevention of disease: a matter of aneurysmic proportions. J Clin Invest. 2010; 120(2):403-7. PMC: 2810090. DOI: 10.1172/JCI42014. View

Akbar Ali O, Chapman M, Nguyen T, Chirkov Y, Heresztyn T, Mundisugih J . Interactions between inflammatory activation and endothelial dysfunction selectively modulate valve disease progression in patients with bicuspid aortic valve. Heart. 2014; 100(10):800-5. DOI: 10.1136/heartjnl-2014-305509. View

Prasad K, Sarkar A, Zafar M, Shoker A, Moselhi H, Tranquilli M . Advanced Glycation End Products and its Soluble Receptors in the Pathogenesis of Thoracic Aortic Aneurysm. Aorta (Stamford). 2016; 4(1):1-10. PMC: 5068493. DOI: 10.12945/j.aorta.2015.15.018. View

Takeda N, Hara H, Fujiwara T, Kanaya T, Maemura S, Komuro I . TGF-β Signaling-Related Genes and Thoracic Aortic Aneurysms and Dissections. Int J Mol Sci. 2018; 19(7). PMC: 6073540. DOI: 10.3390/ijms19072125. View

Bendeck M, Keeley F, Langille B . Perinatal accumulation of arterial wall constituents: relation to hemodynamic changes at birth. Am J Physiol. 1994; 267(6 Pt 2):H2268-79. DOI: 10.1152/ajpheart.1994.267.6.H2268. View

10.

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

11.

Borger M, Fedak P, Stephens E, Gleason T, Girdauskas E, Ikonomidis J . The American Association for Thoracic Surgery consensus guidelines on bicuspid aortic valve-related aortopathy: Full online-only version. J Thorac Cardiovasc Surg. 2018; 156(2):e41-e74. PMC: 6413866. DOI: 10.1016/j.jtcvs.2018.02.115. View

12.

Lindsey J, Cipollone F, Abdullah S, McGuire D . Receptor for advanced glycation end-products (RAGE) and soluble RAGE (sRAGE): cardiovascular implications. Diab Vasc Dis Res. 2009; 6(1):7-14. DOI: 10.3132/dvdr.2009.002. View

13.

Parks W, Roby J, Wu L, Grosso L . Cellular expression of tropoelastin mRNA splice variants. Matrix. 1992; 12(2):156-62. DOI: 10.1016/s0934-8832(11)80057-0. View

14.

Fondard O, Detaint D, Iung B, Choqueux C, Adle-Biassette H, Jarraya M . Extracellular matrix remodelling in human aortic valve disease: the role of matrix metalloproteinases and their tissue inhibitors. Eur Heart J. 2005; 26(13):1333-41. DOI: 10.1093/eurheartj/ehi248. View

15.

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

16.

Goracy I, Grudniewicz S, Safranow K, Ciechanowicz A, Jakubiszyn P, Goracy A . Genetic Polymorphisms of , , , and in Polish Patients with Thoracic Aortopathy. Dis Markers. 2020; 2020:9567239. PMC: 7532390. DOI: 10.1155/2020/9567239. View

17.

Sarkar A, Prasad K, Ziganshin B, Elefteriades J . Reasons to Investigate the Soluble Receptor for Advanced Glycation End-Product (sRAGE) Pathway in Aortic Disease. Aorta (Stamford). 2016; 1(3):210-7. PMC: 4750919. DOI: 10.12945/j.aorta.2013.13-047. View

18.

Scola L, Giarratana R, Marinello V, Cancila V, Pisano C, Ruvolo G . Polymorphisms of Pro-Inflammatory IL-6 and IL-1β Cytokines in Ascending Aortic Aneurysms as Genetic Modifiers and Predictive and Prognostic Biomarkers. Biomolecules. 2021; 11(7). PMC: 8301826. DOI: 10.3390/biom11070943. View

19.

Diekmann F, Chouvarine P, Sallmon H, Meyer-Kobbe L, Kieslich M, Plouffe B . Soluble Receptor for Advanced Glycation End Products (sRAGE) Is a Sensitive Biomarker in Human Pulmonary Arterial Hypertension. Int J Mol Sci. 2021; 22(16). PMC: 8395319. DOI: 10.3390/ijms22168591. View

20.

Forte A, Bancone C, Cobellis G, Buonocore M, Santarpino G, Fischlein T . A Possible Early Biomarker for Bicuspid Aortopathy: Circulating Transforming Growth Factor β-1 to Soluble Endoglin Ratio. Circ Res. 2017; 120(11):1800-1811. DOI: 10.1161/CIRCRESAHA.117.310833. View