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

**Authors:** Brooke R. Shepley, Nick J. Lester, Lana H. Yacoub, Anthony R. Bain

PMC · DOI: 10.1515/teb-2025-0006 · Translational Exercise Biomedicine · 2025-05-28

## TL;DR

This study found that Notch1 activity in healthy adults is linked to aerobic fitness but not to immediate blood vessel dilation.

## Contribution

The study reveals a novel link between Notch1 activity and aerobic fitness in healthy individuals.

## Key findings

- Notch1 extracellular domain (NECD) changes were significantly correlated with aerobic fitness (V̇O2 peak).
- NECD and VEGF concentrations were not related to flow-mediated dilation (FMD) responses.
- No acute changes in NECD or VEGF were observed during FMD testing.

## 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.

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).

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.

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.

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.

## Linked entities

- **Genes:** NOTCH1 (notch receptor 1) [NCBI Gene 4851]
- **Proteins:** VEGFA (vascular endothelial growth factor A), N (Notch)

## Full-text entities

- **Genes:** NOTCH1 (notch receptor 1) [NCBI Gene 4851] {aka AOS5, AOVD1, TAN1, hN1}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12239093/full.md

## References

36 references — full list in the complete paper: https://tomesphere.com/paper/PMC12239093/full.md

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Source: https://tomesphere.com/paper/PMC12239093