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eNOS plays essential roles in the developing heart and aorta linked to disruption of Notch signalling

Lookup NU author(s): Dr Lorraine Eley, Dr Rachel Richardson, Ahlam Alqahtani, Dr Bill Chaudhry, Professor Deborah HendersonORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2024. Published by The Company of Biologists Ltd. eNOS (NOS3) is the enzyme that generates nitric oxide, a signalling molecule and regulator of vascular tone. Loss of eNOS function is associated with increased susceptibility to atherosclerosis, hypertension, thrombosis and stroke. Aortopathy and cardiac hypertrophy have also been found in eNOS null mice, but their aetiology is unclear. We evaluated eNOS nulls before and around birth for cardiac defects, revealing severe abnormalities in the ventricular myocardium and pharyngeal arch arteries. Moreover, in the aortic arch, there were fewer baroreceptors, which sense changes in blood pressure. Adult eNOS null survivors showed evidence of cardiac hypertrophy, aortopathy and cartilaginous metaplasia in the periductal region of the aortic arch. Notch1 and neuregulin were dysregulated in the forming pharyngeal arch arteries and ventricles, suggesting that these pathways may be relevant to the defects observed. Dysregulation of eNOS leads to embryonic and perinatal death, suggesting mutations in eNOS are candidates for causing congenital heart defects in humans. Surviving eNOS mutants have a deficiency of baroreceptors that likely contributes to high blood pressure and may have relevance to human patients who suffer from hypertension associated with aortic arch abnormalities.

Publication metadata

Author(s): Eley L, Richardson RV, Alqahtani A, Chaudhry B, Henderson DJ

Publication type: Article

Publication status: Published

Journal: Disease Models & Mechanisms

Year: 2024

Volume: 17

Issue: 1

Online publication date: 22/01/2024

Acceptance date: 12/12/2023

Date deposited: 07/02/2024

ISSN (print): 1754-8403

ISSN (electronic): 1754-8411

Publisher: The Company of Biologists


DOI: 10.1242/dmm.050265

PubMed id: 38111957


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Funder referenceFunder name
RG/19/2/34256British Heart Foundation