Association of circulating Notch1 and VEGF with flow-mediated dilation and aerobic fitness in healthy adults.

Abstract

Notch1 is a mechanosensitive endothelial receptor that responds to vascular wall shear stress. However, data on Notch1 activity in humans remains limited, particularly regarding its role in endothelial function.

Objectives: Accordingly, the purpose of this study was to determine whether Notch1 is associated with the flow-mediated dilatory (FMD) response and whether it is related to aerobic fitness. A secondary purpose was to determine whether Notch1 is related to concentrations of vascular endothelial growth factor (VEGF).

Methods: Sixteen (8M/8F) young (20-30 yrs old) and healthy (BMI: 25 ± 4.2 kg/m², blood pressure: 117 ± 11.63/69 ± 11.25 mmHg) adults participated in the study. Aerobic fitness was determined by cycle V̇O₂ peak. An FMD was performed on the brachial artery, and blood samples were taken from an antecubital vein at rest (baseline) and 1 min after cuff deflation (to align with peak vessel dilation). Concentrations of Notch1 extracellular domain (NECD) and VEGF were determined from plasma using enzyme-linked immunosorbent assays.

Results: In contrast to our hypothesis, concentrations of NECD and VEGF did not change throughout the FMD and were unrelated to allometrically scaled FMD values (p all>0.05). Likewise, there was no relationship between changes in NECD and VEGF (p=0.331, r=0.127). However, the change in NECD across the FMD was moderately (r=0.515) and significantly (p=0.024) correlated with V̇O₂ peak.

Conclusions: These novel data indicate that in healthy young adults, Notch1 activity is linked to aerobic fitness but may not be acutely involved in the shear-mediated vasodilatory response.