Associations of Angiotensin‐Converting Enzyme 2 Activity With Markers of Endothelial Dysfunction and Oxidative Stress in Young Healthy Adults: The African‐PREDICT Study
4 affiliations
- 1North‐West University
- 2Austin Health, University of Melbourne, Heidelberg
- 3University of New South Wales, The George Institute for Global Health
- 4University of Massachusetts Boston
Abstract
Background Activation of the renin–angiotensin–aldosterone‐system plays a major role in the pathogenesis of cardiovascular disease through, among others, endothelial dysfunction and oxidative stress. Circulating ACE2 (angiotensin‐converting enzyme 2) is emerging as a biomarker of cardiovascular disease risk; however, its role in younger populations is not well‐established. This study aimed to investigate sex differences in serum ACE2 activity and associations with endothelial dysfunction and oxidative stress‐related markers in young, apparently healthy men and women. Methods In this cross‐sectional study, we included 1134 young (aged 20–30 years) men (n=557) and women (n=577). Serum ACE2 activity was measured using a validated fluorometric assay. We analyzed markers of endothelial dysfunction, oxidative stress, and antioxidant capacity. We performed a 2‐sample t test and Mann‐Whitney U test. We applied multivariable‐adjusted Tobit regression analysis to account for left truncation. Results Men had higher ACE2 activity than women ( P <0.001). After multiple adjustments for covariates, ACE2 activity was positively associated with von Willebrand factor ( P =0.006), and a disintegrin‐like metalloproteinase with thrombospondin motif type 1 member 13 ( P =0.019) in men. Among women, ACE2 activity was negatively associated with asymmetric dimethylarginine ( P =0.043) and superoxide dismutase ( P =0.004). Conclusions Serum ACE2 activity was higher in men than women and showed sex‐specific associations with endothelial dysfunction and oxidative stress‐related markers. Our results suggest an association between ACE2 shedding and pathophysiological processes associated with alterations in endothelial integrity and early endothelial dysfunction, which may be influenced by sex. This highlights the role of circulating ACE2 as a potential early biomarker of cardiovascular disease risk in young adults. Registration URL: https://clinicaltrials.gov ; Unique identifier: NCT03292094.
Related
- Deer antler tip cell culture supernatant restores endothelial barrier function and angiotensin converting enzyme 2/endothelial nitric oxide synthase nitric oxide signaling impaired by Porphyromonas gingivalis lipopolysaccharide.
- Prehypertension and Endothelial Dysfunction: The Role of Oxidative Stress
- Angiotensin-Converting Enzyme in Patients With Early-Stage Psychosis
- Case-control study on the association of angiotensin-converting enzyme gene I/D rs4646944 single nucleotide polymorphism and young-onset cryptogenic ischemic stroke in an Algerian cohort Estudo de caso-controle sobre associação do polimorfismo de nucleotídeo único I/D rs4646944 do gene da enzima conversora de angiotensina e acidente vascular isquêmico criptogênico de início precoce em coorte argelina
- Vascular Remodelling in Idiopathic Nephrotic Syndrome with Administration of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers
BibTeX
@article{maugana2026associations,
title = {{Associations of Angiotensin‐Converting Enzyme 2 Activity With Markers of Endothelial Dysfunction and Oxidative Stress in Young Healthy Adults: The African‐PREDICT Study}},
author = {Vuledzani Felicia Maugana and Louise M. Burrell and Sheila K. Patel and Catharina Martha C. Mels and Aletta Elisabeth Schutte and Maserame Cleopatra Mokhaneli and Nonkululeko Hellen Navise and Thabisile Mpofana and Philimon N. Gona and Lebo Francina Gafane‐Matemane},
journal = {Journal of the American Heart Association},
year = {2026},
month = oct,
doi = {10.1161/jaha.125.047345},
url = {https://www.ahajournals.org/doi/10.1161/JAHA.125.047345},
note = {CC BY},
}
RIS
TY - JOUR
TI - Associations of Angiotensin‐Converting Enzyme 2 Activity With Markers of Endothelial Dysfunction and Oxidative Stress in Young Healthy Adults: The African‐PREDICT Study
AU - Vuledzani Felicia Maugana
AU - Louise M. Burrell
AU - Sheila K. Patel
AU - Catharina Martha C. Mels
AU - Aletta Elisabeth Schutte
AU - Maserame Cleopatra Mokhaneli
AU - Nonkululeko Hellen Navise
AU - Thabisile Mpofana
AU - Philimon N. Gona
AU - Lebo Francina Gafane‐Matemane
PY - 2026
DA - 2026/10/20
JO - Journal of the American Heart Association
DO - 10.1161/jaha.125.047345
UR - https://www.ahajournals.org/doi/10.1161/JAHA.125.047345
AB - Background Activation of the renin–angiotensin–aldosterone‐system plays a major role in the pathogenesis of cardiovascular disease through, among others, endothelial dysfunction and oxidative stress. Circulating ACE2 (angiotensin‐converting enzyme 2) is emerging as a biomarker of cardiovascular disease risk; however, its role in younger populations is not well‐established. This study aimed to investigate sex differences in serum ACE2 activity and associations with endothelial dysfunction and oxidative stress‐related markers in young, apparently healthy men and women. Methods In this cross‐sectional study, we included 1134 young (aged 20–30 years) men (n=557) and women (n=577). Serum ACE2 activity was measured using a validated fluorometric assay. We analyzed markers of endothelial dysfunction, oxidative stress, and antioxidant capacity. We performed a 2‐sample t test and Mann‐Whitney U test. We applied multivariable‐adjusted Tobit regression analysis to account for left truncation. Results Men had higher ACE2 activity than women ( P <0.001). After multiple adjustments for covariates, ACE2 activity was positively associated with von Willebrand factor ( P =0.006), and a disintegrin‐like metalloproteinase with thrombospondin motif type 1 member 13 ( P =0.019) in men. Among women, ACE2 activity was negatively associated with asymmetric dimethylarginine ( P =0.043) and superoxide dismutase ( P =0.004). Conclusions Serum ACE2 activity was higher in men than women and showed sex‐specific associations with endothelial dysfunction and oxidative stress‐related markers. Our results suggest an association between ACE2 shedding and pathophysiological processes associated with alterations in endothelial integrity and early endothelial dysfunction, which may be influenced by sex. This highlights the role of circulating ACE2 as a potential early biomarker of cardiovascular disease risk in young adults. Registration URL: https://clinicaltrials.gov ; Unique identifier: NCT03292094.
SN - 2047-9980
ER -