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

Int J Mol Sci. 2024 Sep 30;25(19):10538. doi: 10.3390/ijms251910538.

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.

Keywords: aortic aneurysm; aortic dilatation; bicuspid aortic valve; children; matrix metalloproteinase.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Aorta / diagnostic imaging
  • Aorta / pathology
  • Aortic Valve* / abnormalities
  • Aortic Valve* / diagnostic imaging
  • Aortic Valve* / pathology
  • Bicuspid Aortic Valve Disease* / diagnostic imaging
  • Biomarkers* / blood
  • Child
  • Child, Preschool
  • Dilatation, Pathologic
  • Female
  • Heart Valve Diseases* / blood
  • Humans
  • Male
  • Matrix Metalloproteinase 1 / blood
  • Matrix Metalloproteinase 2 / blood
  • Matrix Metalloproteinase 9 / blood
  • Matrix Metalloproteinases / blood
  • Matrix Metalloproteinases / metabolism
  • Tissue Inhibitor of Metalloproteinase-1* / blood

Substances

  • Tissue Inhibitor of Metalloproteinase-1
  • Biomarkers
  • TIMP1 protein, human
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 1