Clinical and Applied Thrombosis/Hemostasis (Dec 2024)
Vascular Endothelial Dysfunction and Immunothrombosis in the Pathogenesis of Atrial Fibrillation
Abstract
Atrial Fibrillation (AF) induces proinflammatory processes which incite vascular endothelial activation and dysfunction. This study seeks to examine the potential relationship between various endothelial, inflammatory, thrombotic, and renin-angiotensin-system (RAS) biomarkers in AF patients. Blood samples were from AF patients (n = 110) prospectively enrolled in this study prior to their first AF ablation. Control plasma samples (n = 100) were used as reference. All samples were analyzed for endothelial (NO, ICAM-1, VEGF, TF, TFPI, TM, Annexin V), inflammatory (IL-6, TNFα, CRP), thrombotic (vWF, tPA, PAI-1, TAFI, D-dimer), and RAS (Renin, Ang-II) biomarkers using ELISA methods. Biomarker average comparisons and Spearman correlations were performed. AF patients showed varying levels of biomarker increase compared to controls. We observed a significant decrease of Ang-II in the AF population relative to controls when stratified for the use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) upon study enrollment. AF patients showed statistically significant correlations between the following biomarkers: TNFα vs IL-6 (r s = 0.317, p = .004), ICAM-1 vs TNFα (r s = 0.527, p = .012), Annexin V vs VEGF (r s = 0.620, p < .001), CRP vs VEGF (r s = 0.342, p = .031), Ang-II vs tPA (r s = −0.592, p = .010), and tPA vs PAI-1 (r s = 0.672, p < .001). Our study demonstrated significant elevation of endothelial, inflammatory, and thrombotic biomarkers in AF patients compared to controls, with significant correlations between these biomarkers in the AF population. Future investigations are required to better elucidate the mechanistic pathways that lead to endothelial dysfunction and thromboinflammation in AF. This may provide novel therapeutic targets, that in addition to current anticoagulation practices, can best curtail thrombogenicity in AF.