Common Biomarkers of Endothelial Dysfunction Across Highly Prevalent Diseases with Cardiovascular Risk: Functional Characterization and Prognostic Implications

Endothelial dysfunction (ED) arises in multiple pathologies, and its severity correlates with disease progression. Common ED biomarkers could provide prognostic value for associated complications. This study aims to identify shared ED biomarkers and assess their prognostic significance. Endothelial cells in culture (human microvascular endothelial cells, HMEC-1) were exposed to sera from patients in five disease groups (n = 20 patients/group)—liver cirrhosis with portal hypertension, idiopathic pulmonary arterial hypertension, placental disorders such as intrauterine growth restriction, coronary artery disease with acute myocardial infarction, and chronic kidney disease—or matched controls, in the absence/presence of anti-inflammatory (apixaban) and antioxidant (EUK134) compounds. We explored changes in: VCAM-1, ICAM-1, eNOS, VWF, extracellular matrix thrombogenicity, and reactive oxygen species (ROS). In serum samples, proteomics and metabolomics analyses (including lipids, amino acids, and polar metabolites) were performed through an extraction protocol to identify common ED biomarkers. Expression of VCAM-1, ICAM-1, VWF, platelet adhesion, and ROS increased in most groups versus controls (p < 0.05). Both drugs decreased all biomarker levels except eNOS (n = 6 for in vitro experiments). For serum ED biomarkers, 18 metabolites and 24 proteins showed AUC-ROC and hit rates >77.5%, and six metabolites were associated with event-free survival. These diseases share ED driven by systemic inflammatory, oxidative, and metabolic stress, are partially reversible in vitro, and are linked to biomarkers associated with clinical outcomes. Overall, ED emerges as a modifiable pathological axis with potential prognostic value.

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Journal
International Journal of Molecular Sciences
Published
2026-04-25
DOI
https://doi.org/10.3390/ijms27093829
Primary Topic
Nitric Oxide and Endothelin Effects
Type
article
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article

Common Biomarkers of Endothelial Dysfunction Across Highly Prevalent Diseases with Cardiovascular Risk: Functional Characterization and Prognostic Implications

Arturo Pereira, Elena Cuadrado‐Payán, Juan Carlos García‐Pagán, Olga Tura-Ceide et al.
International Journal of Molecular Sciences
Nitric Oxide and Endothelin Effects
article

Common Biomarkers of Endothelial Dysfunction Across Highly Prevalent Diseases with Cardiovascular Risk: Functional Characterization and Prognostic Implications

Arturo Pereira, Elena Cuadrado‐Payán, Juan Carlos García‐Pagán, Olga Tura-Ceide, Jordi Rovira, Isabel Galcerán, Ginés Escolar, Ana Paula Dantas, Sergi Torramadé‐Moix, Héctor García‐Calderó, Erica Lafoz, Julia Martínez-Sánchez, F. Crispi, Aleix Cases, Eduard Gratacós, Virginia Hernández–Gea, Maribel Díaz‐Ricart, Fritz Diekmann, A B Moreno-Castaño, Joan Albert Barberà, Lida Maria Rodas
article en

Abstract

Endothelial dysfunction (ED) arises in multiple pathologies, and its severity correlates with disease progression. Common ED biomarkers could provide prognostic value for associated complications. This study aims to identify shared ED biomarkers and assess their prognostic significance. Endothelial cells in culture (human microvascular endothelial cells, HMEC-1) were exposed to sera from patients in five disease groups (n = 20 patients/group)—liver cirrhosis with portal hypertension, idiopathic pulmonary arterial hypertension, placental disorders such as intrauterine growth restriction, coronary artery disease with acute myocardial infarction, and chronic kidney disease—or matched controls, in the absence/presence of anti-inflammatory (apixaban) and antioxidant (EUK134) compounds. We explored changes in: VCAM-1, ICAM-1, eNOS, VWF, extracellular matrix thrombogenicity, and reactive oxygen species (ROS). In serum samples, proteomics and metabolomics analyses (including lipids, amino acids, and polar metabolites) were performed through an extraction protocol to identify common ED biomarkers. Expression of VCAM-1, ICAM-1, VWF, platelet adhesion, and ROS increased in most groups versus controls (p < 0.05). Both drugs decreased all biomarker levels except eNOS (n = 6 for in vitro experiments). For serum ED biomarkers, 18 metabolites and 24 proteins showed AUC-ROC and hit rates >77.5%, and six metabolites were associated with event-free survival. These diseases share ED driven by systemic inflammatory, oxidative, and metabolic stress, are partially reversible in vitro, and are linked to biomarkers associated with clinical outcomes. Overall, ED emerges as a modifiable pathological axis with potential prognostic value.

International Journal of Molecular SciencesVol. 27(9)
Hospital Sant Joan de Déu Barcelona (ES), Instituto de Salud Carlos III (ES), Centre for Biomedical Network Research on Rare Diseases (ES), Institut d'Investigació Biomèdica de Girona (ES), Hospital Clínic de Barcelona (ES), Hospital Santa Caterina (ES), Institute for Research in Biomedicine (ES), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (ES), Fundació Clínic per a la Recerca Biomèdica (ES), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES), Universitat de Barcelona (ES)
Instituto de Salud Carlos III, Departament de Recerca i Universitats, Generalitat de Catalunya
Good health and well-being
Openalex Percentile: Top 7%
Nitric Oxide and Endothelin Effects
DOIOpen Access PDFOpenAlex
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