Common Biomarkers of Endothelial Dysfunction Across Highly Prevalent Diseases with Cardiovascular Risk: Functional...

Area of Science:

• Cardiovascular Biology
• Pathophysiology
• Biomarker Discovery

Background:

• Endothelial dysfunction (ED) is implicated in numerous pathologies, with severity correlating to disease progression.
• Identifying common ED biomarkers may offer prognostic insights into associated complications.

Purpose of the Study:

• To identify shared ED biomarkers across diverse diseases.
• To evaluate the prognostic significance of these biomarkers.
• To investigate the reversibility of ED in vitro.

Main Methods:

• Human microvascular endothelial cells (HMEC-1) were treated with patient sera from liver cirrhosis, pulmonary arterial hypertension, placental disorders, coronary artery disease, and chronic kidney disease groups.
• Analyzed changes in VCAM-1, ICAM-1, eNOS, VWF, extracellular matrix thrombogenicity, and reactive oxygen species (ROS).
• Utilized proteomics and metabolomics on serum samples to identify common ED biomarkers, assessing their diagnostic and prognostic capabilities.

Main Results:

• Increased expression of VCAM-1, ICAM-1, VWF, platelet adhesion, and ROS was observed in most disease groups compared to controls.
• Anti-inflammatory and antioxidant compounds partially reversed these biomarker changes in vitro.
• Proteomics and metabolomics identified 18 metabolites and 24 proteins with high diagnostic accuracy (AUC-ROC >77.5%), and six metabolites correlated with event-free survival.

Conclusions:

• Multiple pathologies share a common endothelial dysfunction (ED) axis driven by inflammatory, oxidative, and metabolic stress.
• ED is partially reversible in vitro and is associated with specific biomarkers that hold prognostic value.
• Endothelial dysfunction represents a modifiable pathological pathway with potential clinical utility for predicting disease outcomes.