Iranian Heart Journal

Iranian Heart Journal

Flow-Mediated Arterial Dilatation, Hypertension, and ACE2 in Adolescent Obesity: A Cross-Sectional Study

Document Type : Original Article

Authors
1 Department of Cardiology and Vascular Medicine, Faculty of Medicine Universitas Airlangga - Dr. Soetomo General Academic Hospital, Surabaya, Indonesia.
2 Division of Nutrition and Metabolic Diseases, Childhealth Department, Faculty of Medicine Universitas Airlangga - Dr. Soetomo General Academic Hospital, Surabaya, Indonesia.
Abstract
Background: Endothelial dysfunction is a significant mechanism underlying various cardiovascular diseases. In the context of COVID-19, soluble angiotensin-converting enzyme 2 (sACE2) and flow-mediated dilation (FMD) are linked to endothelial dysfunction. This study aimed to evaluate sACE2 and FMD levels among obese and non-obese Indonesian adolescents.
 
Methods: This study involved 72 Indonesian adolescents, with a mean age of 195 months (range = 178–217). The majority of participants were male (61%). They were divided into 3 groups: those with obesity and hypertension (n=21), those with obesity without hypertension (n=19), and non-obese individuals (n=32). FMD assessment involved measuring the brachial artery using supra-systolic pressure applied to the forearm for 5 minutes. Further, sACE2 levels were determined using the Sandwich ELISA method.
 
Results: The median level of sACE2 was 25.4 pg/mL, with a range of 0.25 to 181.8 pg/mL. Nonetheless, no statistically significant differences in sACE2 levels were observed between the three groups (P = 0.464). Although descriptive statistics indicated that FMD values were higher in normal adolescents, no significant differences were found in FMD values between the groups: those with obesity and hypertension (9.1 ± 5%), those with obesity without hypertension (8.3 ± 3.1%), and normal adolescents (10.9 ± 6.2%) (P = 0.159). Furthermore, the comparison of sACE2 levels between the groups with and without endothelial dysfunction revealed no differences (P = 0.95). There was also no statistically significant correlation between sACE2 levels and FMD (P = 0.59, r = 0.064).
 
Conclusions: Our results showed no differences in sACE2 and FMD values between obese and non-obese Indonesian adolescents, regardless of hypertension status. Additionally, the correlation between endothelin-1 and FMD is not significant in this population of Indonesian adolescents. (Iranian Heart Journal 2025; 26(3): 51-58)
Keywords

  1. Lilly, L.S. Pathophysiology of Heart Disease: An Introduction to Cardiovascular Medicine. Philadelphia: Wolters Kluwer Medknow Publications; 2020.
  2. Yeung, M.L., Teng, J.L.L., Jia, L., et al. Soluble ACE2-Mediated Cell Entry of SARS-CoV-2 Via Interaction with Proteins Related to The Renin-Angiotensin System. Cell., 2021,;184(8),2212-2228.e12.
  3. Zheng, M.. ACE2 And COVID-19 Susceptibility and Severity. Aging Dis., 2022,; 13(2),360–72.
  4. Xu, S. wen., Ilyas, I., Weng, J. ping. Endothelial Dysfunction In COVID-19: An Overview of Evidence, Biomarkers, Mechanisms and Potential Therapies. Acta Pharmacol Sin., 2023,; 44(4),695–709.
  5. Nagatomo, I., Nakanishi, K., Yamamoto, R., et al. Soluble Angiotensin-Converting Enzyme 2 Association with Lipid Metabolism. Front Med., 2022,; 9(August),1–6.
  6. Bellien, J., Iacob, M., Monteil, C., et al. Physiological Role of Endothelin-1in Flow-Mediated Vasodilatation in Humans and Impact of Cardiovascular Risk Factors. J Hypertens., 2017,;35(6),1204–12.
  7. Mućka, S., Miodońska, M., Jakubiak, G.K., et al. Endothelial Function Assessment by Flow-Mediated Dilation Method: A Valuable Tool in The Evaluation of The Cardiovascular System. Int J Environ Res Public Health., 2022,;19(18),.
  8. Guz, G., Demirgan, S. Lower Brachial Artery Flow-Mediated Dilation is Associated with A Worse Prognosis and More Lung Parenchymal Involvement in Covid-19: Prospective Observational Study. Med (United States)., 2022,; 101(33),E30001.
  9. Cole, T.J., Bellizzi, M.C., Flegal, K.M., Dietz, W.H. Establishing A Standard Definition for Child Overweight and Obesity Worldwide: International Survey. Br Med J., 2000,; 320(7244),1240–3.
  10. Saputra, P.B.T., Lamara, A.D.L., Saputra, M.E., et al. Diagnosis dan Terapi Non-Farmakologis Hipertensi. Cermin Dunia Kedokt., 2023,; 50(6),322–30.
  11. Maruhashi, T., Kajikawa, M., Kishimoto, S., et al. Diagnostic Criteria of Flow-Mediated Vasodilation for Normal Endothelial Function and Nitroglycerin-Induced Vasodilation for Normal Vascular Smooth Muscle Function of The Brachial Artery. J Am Heart Assoc., 2020,; 9(2),1–13.
  12. Saputra, P.B.T., Izzati, N., Rosita, P.E., et al. National Health Insurance Based Telemedicine Application for Hypertension Management in Primary Level of Health Facilities. J Community Med Public Heal Res., 2021,; 2(1),32.
  13. Oktaviono, Y.H., Dyah Lamara, A., Saputra, P.B.T., et al. Roles of Trimethylamine-N-Oxide in Atherosclerosis and Its Potential Therapeutic Aspect: A Literature Review. Biomol Biomed., 2023,; 1–13.
  14. Tri Saputra, P.B., Yolanda, S., Dwi Purwati, D., Sulistiawati. The Roles of Social Media in Hypertension Management Programs. Cermin Dunia Kedokt., 2022,; 49(8),469–73.
  15. Dadras, O., Afsahi, A.M., Pashaei, Z., et al. The Relationship between COVID-19 Viral Load and Disease Severity: A Systematic Review. Immunity, Inflamm Dis., 2022,; 10(3),1–25.
  16. Emilsson, V., Gudmundsson, E.F., Aspelund, T., et al. Serum Levels of ACE2 are Higher in Patients with Obesity and Diabetes. Obes Sci Pract., 2021,; 7(2),239–43.
  17. Wambier, C.G., Goren, A., Ossimetha, A., Nau, G., Qureshi, A. Androgen-Driven COVID-19 Pandemic Theory. SSRN Electron J., 2020,; (April),.
  18. Glaser, R., Dimitrakakis, C. Testosterone Therapy in Women: Myths and Misconceptions. Maturitas Internet., 2013,; 74(3),230–4. Available from: Http://Dx.Doi.Org/10.1016/J.Maturitas.2013.01.003
  19. Kataoka, T., Hotta, Y., Maeda, Y., Kimura, K. Testosterone Deficiency Causes Endothelial Dysfunction Via Elevation of Asymmetric Dimethylarginine and Oxidative Stress in Castrated Rats. J Sex Med Internet., 2017,; 14(12),1540–8. Available from: Https://Doi.Org/10.1016/J.Jsxm.2017.11.001
  20. Kataoka, T., Fukamoto, A., Hotta, Y., et al. Effect of High Testosterone Levels on Endothelial Function in Aorta and Erectile Function in Rats. Sex Med Internet., 2022,; 10(5), 100550. Available from: Https://Doi.Org/10.1016/J.Esxm.2022.100550