MON-216 Association of Serum Irisin Levels with Endothelial Dysfunction Markers in a Model of Endothelial Cells Challenged with Serum from Patients with Diabetes Mellitus and Metabolic Syndrome

Abstract Disclosure: E. Luna Ceron: None. A. Casillas Fikentscher: None. S. Duvvuru: None. E.C. Gonzalez Castillo: None. P. Segura Medina: None. L. Elizondo Montemayor: None. Background: Endothelial dysfunction is a key mechanism in cardiovascular diseases and can result from metabolic disorders. Irisin, an adipomyokine, has shown potential in preventing endothelial dysfunction by reducing oxidative stress, promoting nitric oxide (NO) production, and enhancing endothelial cell viability. However, existing studies focus on single factors affecting the endothelium, lacking representation of the complex metabolic environment in humans. Additionally, data on circulating irisin levels and endothelial dysfunction markers in pediatric populations with Type 2 Diabetes Mellitus (T2DM) and Metabolic Syndrome (MetS) is limited. This study aimed to explore the association between serum irisin levels and endothelial dysfunction markers using an in vitro model of human umbilical vein endothelial cells (HUVECs) exposed to serum from pediatric patients with T2DM and MetS. Methods: Serum samples were collected from 55 pediatric patients (ages 6 to 16), categorized into T2DM (n=21), MetS (n=18), and healthy controls (n=16). Serum irisin levels and concentrations of soluble leukocyte adhesion molecules (sICAM1, sICAM2, sNCAM, sVCAM1, sL-Selectin, sE-Selectin, sP-Selectin) were measured. HUVECs were treated with matched patient serum for 24 hours, and cell viability and endothelial NO production were assessed. Results: Results showed significantly lower serum irisin levels in the MetS and T2DM groups compared to healthy controls (p=0.004). HUVECs exposed to serum from T2DM and MetS patients had lower endothelial NO production (p < 0.05), reduced cell viability (p < 0.01), and higher rates of late apoptotic (p < 0.01) and necrotic cells (p < 0.05) compared to those treated with serum from healthy controls. Positive correlations were found between serum irisin levels and NO production (R=0.27, p<0.05) and cell viability (R=0.37, p<0.05). Negative correlations were observed between irisin levels and late apoptotic (R=-0.41, p<0.05) and necrotic (R=-0.32, p<0.05) cell rates. Additionally, irisin levels negatively correlated with sICAM2 (R=-0.3, p<0.05) and sVCAM (R=-0.3, p<0.05). Conclusions: In conclusion, these results suggest that irisin may protect endothelial integrity under adverse metabolic conditions by maintaining NO production, sustaining cell viability, and reducing late apoptosis. Low circulating irisin levels in T2DM and MetS patients may contribute to endothelial dysfunction, marked by reduced cell functionality and increased expression of leukocyte adhesion molecules. Presentation: Monday, July 14, 2025