Serum levels of VEGF and VE-cadherin in patients with obstructive sleep apnea and their clinical value_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

LI Mengru ¹ , ZHU Xueyan ¹ , JI Lei ² , JI Guijuan ² , ZHAO Ling ² , CHEN Bi ² ,  ZHANG Wenhui ²

1. Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221000, P. R. China;
2. Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221000, P. R. China;

Corresponding author：

ZHANG Wenhui, Email: xzzyz2000@126.com

Keywords：

Obstructive sleep apnea; vascular endothelial growth factor; vascular endothelial cadherin; continuous positive airway pressure

DOI：

10.7507/1671-6205.202503071

Video：

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Objective To evaluate the correlation of vascular endothelial growth factor (VEGF) and vascular endothelial cadherin (VE-Cadherin) in serum with the severity of obstructive sleep apnea (OSA) and explore their clinical value in OSA. Methods A total of 90 patients with OSA admitted to the Sleep Monitoring Center of the Affiliated Hospital of Xuzhou Medical University from April 2023 to June 2024 were prospectively selected. Based on the apnea-hypopnea index (AHI), the patients were divided into a mild group (5 - 15 times/hour, n=30), a moderate group (>15 - 30 times/hour, n=28), and a severe group (>30 times/hour, n=32). Thirty healthy individuals who underwent physical examinations during the same period were included as a control group. The levels of serum VEGF and soluble VE-Cadherin (sVE) in all subjects were detected by enzyme-linked immunosorbent assay. The differences in serum VEGF and sVE levels among the groups were compared, and the correlations between serum VEGF and sVE levels and sleep parameters were explored. The moderate and severe OSA patients were given 3 months of continuous positive airway pressure (CPAP) treatment, and the changes in sleep parameters and serum VEGF and sVE levels before and after treatment were compared. Results The levels of serum VEGF and sVE in the OSA patients increased with the severity of the disease; the levels of serum VEGF and sVE in the moderate and severe OSA groups were significantly higher than those in the healthy control group and the mild OSA group (P<0.05). The levels of serum VEGF and sVE in the severe OSA group were significantly higher than those in the moderate OSA group (P<0.05). There was no significant difference in the expression levels of serum VEGF or sVE between the mild OSA group and the healthy control group (P>0.05). The sensitivity and specificity of serum VEGF in diagnosing OSA were 65.6% and 93.3%, respectively, with an area under curve (AUC) value of 0.845. The sensitivity and specificity of serum VE-Cadherin in diagnosing OSA were 64.4% and 96.7%, respectively, with an AUC value of 0.835. After 3 months of CPAP treatment, AHI, longest apnea time, serum VEGF and sVE levels in the moderate and severe OSA groups decreased significantly, mean arterial oxygen saturation and lowest arterial oxygen saturation increased significantly (P<0.05). Conclusions The levels of VEGF and VE-Cadherin in serum of OSA patients are significantly elevated and positively correlated with the severity of OSA. Monitoring the changes in the levels of VEGF and VE-Cadherin in serum of OSA patients is helpful for evaluating the therapeutic effect of CPAP.

1.	Meliante PG, Zoccali F, Cascone F, et al. Molecular pathology, oxidative stress, and biomarkers in obstructive sleep apnea. Int J Mol Sci, 2023, 24(6): 5478.
2.	Dodds S, Williams LJ, Roguski A, et al. Mortality and morbidity in obstructive sleep apnoea-hypopnoea syndrome: results from a 30-year prospective cohort study. ERJ Open Res, 2020, 6(3): 57-2020.
3.	Rana D, Torrilus C, Ahmad W, et al. Obstructive sleep apnea and cardiovascular morbidities: a review article. Cureus, 2020, 12(9): e10424.
4.	Redline S, Azarbarzin A, Peker Y. Obstructive sleep apnoea heterogeneity and cardiovascular disease. Nat Rev Cardiol, 2023, 20(8): 560-573.
5.	Zhu D, Kang W, Zhang S, et al. Effect of mandibular advancement device treatment on HIF-1α, EPO and VEGF in the myocardium of obstructive sleep apnea-hypopnea syndrome rabbits. Sci Rep, 2020, 10(1): 13261.
6.	Harki O, Tamisier R, Pépin JL, et al. VE-cadherin cleavage in sleep apnoea: new insights into intermittent hypoxia-related endothelial permeability. Eur Respir J, 2021, 58(4): 2004518.
7.	Osanai S. Clinical Question: Can CPAP suppress cardiovascular events in resistant hypertension patients with obstructive sleep apnea?. Hypertens Res, 2023, 46(6): 1606-1608.
8.	Gottlieb D J, Punjabi NM. Diagnosis and management of obstructive sleep apnea: areview. JAMA, 2020, 323(14): 1389-1400.
9.	Yuan F, Hu Y, Xu F, Feng X. A review of obstructive sleep apnea and lung cancer: epidemiology, pathogenesis, and therapeutic options. Front Immunol, 2024, 15: 1374236.
10.	Bonsignore MR, Mazzuca E, Baiamonte P, et al. REM sleep obstructive sleep apnoea. Eur Respir Rev, 2024, 33(171): 230166.
11.	Fiedorczuk P, Polecka A, Walasek M, et al. Potential diagnostic and monitoring biomarkers of obstructive sleep apnea-umbrella review of meta-analyses. J Clin Med, 2022, 12(1): 60.
12.	Su T, Li C, Zhang Y, et al. Upregulation of HMGB1 promotes vascular dysfunction in the soft palate of patients with obstructive sleep apnea via the TLR4/NF-κB/VEGF pathway. FEBS Open Bio, 2023, 13(2): 246-256.
13.	Goodman MO, Cade BE, Shah NA, et al. Pathway-specific polygenic risk scores identify obstructive sleep apnea-related pathways differentially moderating genetic susceptibility to coronary artery disease. Circ Genom Precis Med, 2022, 15(5): e003535.
14.	Jadon J, Yelin R, Arraf AA, et al. Regulation of aortic morphogenesis and VE-cadherin dynamics by VEGF. Dev Biol, 2023, 497: 1-10.
15.	Zhou W, Liu K. Targeting VEGF-A/VEGFR2 Y949 signaling-mediated vascular permeability alleviates hypoxic pulmonary hypertension. Circulation, 2022, 146(24): 1855-1881.
16.	Burg N, Malpass R, Alex L, et al. Endothelial cell sphingosine 1-phosphate receptor 1 restrains VE-cadherin cleavage and attenuates experimental inflammatory arthritis. JCI Insight, 2024, 9(11): e171467.
17.	Yamamoto K, Takagi Y, Ando K, et al. Rap1 small GTPase regulates vascular endothelial-cadherin-mediated endothelial cell-cell junctions and vascular permeability. Biol Pharm Bull, 2021, 44(10): 1371-1379.
18.	Yang K, Fan M, Wang X, et al. Lactate induces vascular permeability via disruption of VE-cadherin in endothelial cells during sepsis. Sci Adv, 2022, 8(17): eabm8965.
19.	Zolotoff C, Voirin AC. Intermittent hypoxia and its impact on Nrf2/HIF-1α expression and ABC transporters: an in vitro human blood-brain barrier model study. Cell Physiol Biochem, 2020, 54(6): 1231-1248.
20.	Harki O, Bouyon S. Inhibition of vascular endothelial cadherin cleavage prevents elastic fiber alterations and atherosclerosis induced by intermittent hypoxia in the mouse aorta. Int J Mol Sci, 2022, 23(13): 7012.
21.	Roche F, Briançon-Marjollet A, Dematteis M, et al. Early increase in blood-brain barrier permeability in a murine model exposed to fifteen days of intermittent hypoxia. Int J Mol Sci, 2024, 25(5): 3065.
22.	Hein M, Lanquart J P, Loas G, et al. Prevalence and risk factors of moderate to severe obstructive sleep apnea syndrome in insomnia sufferers: a study on 1311 subjects. Respir Res, 2017, 18(1): 135.
23.	Qi JC, Zhang L, Li H, et al. Impact of continuous positive airway pressure on vascular endothelial growth factor in patients with obstructive sleep apnea: a meta-analysis. Sleep Breath, 2019, 23(1): 5-12.

1. Meliante PG, Zoccali F, Cascone F, et al. Molecular pathology, oxidative stress, and biomarkers in obstructive sleep apnea. Int J Mol Sci, 2023, 24(6): 5478.
2. Dodds S, Williams LJ, Roguski A, et al. Mortality and morbidity in obstructive sleep apnoea-hypopnoea syndrome: results from a 30-year prospective cohort study. ERJ Open Res, 2020, 6(3): 57-2020.
3. Rana D, Torrilus C, Ahmad W, et al. Obstructive sleep apnea and cardiovascular morbidities: a review article. Cureus, 2020, 12(9): e10424.
4. Redline S, Azarbarzin A, Peker Y. Obstructive sleep apnoea heterogeneity and cardiovascular disease. Nat Rev Cardiol, 2023, 20(8): 560-573.
5. Zhu D, Kang W, Zhang S, et al. Effect of mandibular advancement device treatment on HIF-1α, EPO and VEGF in the myocardium of obstructive sleep apnea-hypopnea syndrome rabbits. Sci Rep, 2020, 10(1): 13261.
6. Harki O, Tamisier R, Pépin JL, et al. VE-cadherin cleavage in sleep apnoea: new insights into intermittent hypoxia-related endothelial permeability. Eur Respir J, 2021, 58(4): 2004518.
7. Osanai S. Clinical Question: Can CPAP suppress cardiovascular events in resistant hypertension patients with obstructive sleep apnea?. Hypertens Res, 2023, 46(6): 1606-1608.
8. Gottlieb D J, Punjabi NM. Diagnosis and management of obstructive sleep apnea: areview. JAMA, 2020, 323(14): 1389-1400.
9. Yuan F, Hu Y, Xu F, Feng X. A review of obstructive sleep apnea and lung cancer: epidemiology, pathogenesis, and therapeutic options. Front Immunol, 2024, 15: 1374236.
10. Bonsignore MR, Mazzuca E, Baiamonte P, et al. REM sleep obstructive sleep apnoea. Eur Respir Rev, 2024, 33(171): 230166.
11. Fiedorczuk P, Polecka A, Walasek M, et al. Potential diagnostic and monitoring biomarkers of obstructive sleep apnea-umbrella review of meta-analyses. J Clin Med, 2022, 12(1): 60.
12. Su T, Li C, Zhang Y, et al. Upregulation of HMGB1 promotes vascular dysfunction in the soft palate of patients with obstructive sleep apnea via the TLR4/NF-κB/VEGF pathway. FEBS Open Bio, 2023, 13(2): 246-256.
13. Goodman MO, Cade BE, Shah NA, et al. Pathway-specific polygenic risk scores identify obstructive sleep apnea-related pathways differentially moderating genetic susceptibility to coronary artery disease. Circ Genom Precis Med, 2022, 15(5): e003535.
14. Jadon J, Yelin R, Arraf AA, et al. Regulation of aortic morphogenesis and VE-cadherin dynamics by VEGF. Dev Biol, 2023, 497: 1-10.
15. Zhou W, Liu K. Targeting VEGF-A/VEGFR2 Y949 signaling-mediated vascular permeability alleviates hypoxic pulmonary hypertension. Circulation, 2022, 146(24): 1855-1881.
16. Burg N, Malpass R, Alex L, et al. Endothelial cell sphingosine 1-phosphate receptor 1 restrains VE-cadherin cleavage and attenuates experimental inflammatory arthritis. JCI Insight, 2024, 9(11): e171467.
17. Yamamoto K, Takagi Y, Ando K, et al. Rap1 small GTPase regulates vascular endothelial-cadherin-mediated endothelial cell-cell junctions and vascular permeability. Biol Pharm Bull, 2021, 44(10): 1371-1379.
18. Yang K, Fan M, Wang X, et al. Lactate induces vascular permeability via disruption of VE-cadherin in endothelial cells during sepsis. Sci Adv, 2022, 8(17): eabm8965.
19. Zolotoff C, Voirin AC. Intermittent hypoxia and its impact on Nrf2/HIF-1α expression and ABC transporters: an in vitro human blood-brain barrier model study. Cell Physiol Biochem, 2020, 54(6): 1231-1248.
20. Harki O, Bouyon S. Inhibition of vascular endothelial cadherin cleavage prevents elastic fiber alterations and atherosclerosis induced by intermittent hypoxia in the mouse aorta. Int J Mol Sci, 2022, 23(13): 7012.
21. Roche F, Briançon-Marjollet A, Dematteis M, et al. Early increase in blood-brain barrier permeability in a murine model exposed to fifteen days of intermittent hypoxia. Int J Mol Sci, 2024, 25(5): 3065.
22. Hein M, Lanquart J P, Loas G, et al. Prevalence and risk factors of moderate to severe obstructive sleep apnea syndrome in insomnia sufferers: a study on 1311 subjects. Respir Res, 2017, 18(1): 135.
23. Qi JC, Zhang L, Li H, et al. Impact of continuous positive airway pressure on vascular endothelial growth factor in patients with obstructive sleep apnea: a meta-analysis. Sleep Breath, 2019, 23(1): 5-12.

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