Pathogenetic Significance of Endothelial Dysfunction in Pulmonary Hypertension Associated with Congenital Heart Defects in Children: A Modern Literature Review

Abstract

Relevance. Congenital heart defects (CHDs) are among the main causes of pulmonary hypertension and pulmonary vascular disease in children. Particularly in defects associated with systemic-to-pulmonary shunts, a prolonged increase in pulmonary blood flow, pulsatile load, and shear stress alter the functional state of the pulmonary vascular endothelium. As a result, attenuation of vasodilatory and antiproliferative systems, enhancement of vasoconstrictor and proliferative signaling, and progressive vascular remodeling may occur.

Objective. To analyze the main hemodynamic and molecular mechanisms of endothelial dysfunction in the development of pulmonary hypertension associated with CHDs in children based on contemporary scientific data and to evaluate their clinical significance.

Materials and Methods. This article presents a narrative literature review in which scientific studies published in PubMed/MEDLINE and PubMed Central databases between 2020 and 2026 were analyzed.

Results. Endothelial dysfunction is an important mechanism linking hemodynamic load and structural remodeling in pulmonary vascular disease associated with CHDs. Attenuation of the NO–sGC–cGMP and prostacyclin–cAMP pathways, increased endothelin-1 activity, oxidative stress, impaired BMPR2/TGF-β signaling, inflammation, and metabolic alterations promote pathological vascular remodeling. BNP and NT-proBNP are among the most extensively studied biomarkers in pediatric pulmonary hypertension; however, they are not specific markers of endothelial dysfunction.

Conclusion. In pulmonary hypertension associated with CHDs, endothelial dysfunction represents one of the central pathogenetic links in disease initiation and progression. Combined assessment of molecular biomarkers with invasive hemodynamics, PVRI, and right ventricular function represents a promising direction for future research.

Keywords:

Congenital heart defects, children, pulmonary hypertension

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