Journal of Pediatric Perspectives

Journal of Pediatric Perspectives

Dysregulation of MMP and TIMP in Congenital Heart Disease: A Non-Meta-Analysis Systematic Review of Molecular Pathology

Document Type : systematic review

Authors
Yazdan Ghandi 1
Mahbod Soltani 2
Negar Poor Ahmadian 2
Samira Zakeri Shahvari 3
Mohammad Satarzadeh 4
1 Department of Pediatrics, School of Medicine, Arak University of Medical Sciences, Iran, Arak, Iran.
2 School of Medicine, Arak University of Medical Sciences, Iran, Arak, Iran.
3 Assistant of Professor of Pediatrics, School of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
4 Student Research Committee, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
10.22038/jpp.2025.86252.5526
Abstract
Background: Matrix metalloproteinases (MMPs) include a group of factors responsible for cell proliferation, apoptosis, and angiogenesis. Changes in the level of this family are associated with the pathology of structural disorders such as Congenital Heart Disease (CHD). This systematic study assessed previous research to determine the therapeutic potential of MMPs in congenital heart disorders.
Method: This systematic review was written based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, and the principle of nonbias was respected. All the articles from 2014-2024 were extracted from the Web of Science, PubMed and Scopus databases. The study investigated the role of MMPs in the pathology of cardiovascular structural disorders, as well as therapeutic and diagnostic effects of MMP and Tissue inhibitors of metalloproteinases (TIMP) levels.
Results: A total of studies15 were included in our analysis. MMP-1, MMP-2, MMP-3, MMP-8, MMP-10, MMP-13, TIMP-1, and TIMP-4 were found to be significantly elevated in patients with higher degrees of myocardial fibrosis and diastolic heart failure. MMP-2 and MMP-9 levels were significantly increased in hypertensive male patients with bicuspid aortic valve (BAV) and may be associated with an aneurysmal cellular phenotype. MMP-15 plays a critical role in the formation of endocardial cushions, while MMP-1 may serve as a biomarker for ventricular remodeling in patients who have undergone surgery for tetralogy of Fallot (TOF). Elevated levels of TIMP-1, MMP-7 and MMP-12 in patients with postoperative hypoxemia put these children at a higher risk for difficulty weaning off the mechanical ventilator.
Conclusion: Regulating of MMP levels during fetal and postnatal periods could lead to the prevention and treatment of CHD. MMP/TIMP homeostasis is considered the key to CHD treatment and is even an important diagnostic tool.
Keywords
Congenital heart disease
Diagnosis treatment
Matrix metalloproteinases
Systematic review
Tissue inhibitors of metalloproteinases
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Journal of Pediatric Perspectives
Volume 13, Issue 2
February 2025
Pages 19292-19303