Differences of hemorheology indexes and expression of HIF-1α/2α in PI3K/Akt/NF-kB p65 signaling pathway between Tibetan and Han OSAHS patients_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

 LA Zhoucuomao , LI Lingyi , GAO Rui , LIU Hong

Department of Respiratory Medicine, Qinghai University Affiliated Hospital, Xining, Qinghai 810001, P. R. China;

Corresponding author：

LA Zhoucuomao, Email: lazhou12345@163.com

Keywords：

Obstructive sleep apnea hypopnea syndrome; hemorheology; PI3K/AKT/NF-κB p65 signaling pathway; hypoxia-inducible factor-1α; hypoxia-inducible factor-2α

DOI：

10.7507/1671-6205.202007070

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To explore the difference between the hemorheology levels and the expression of hypoxia inducible factor 1α/2α (HIF-1α/2α) in the peripheral blood mononuclear cells of the Tibetan and Han patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods This research recruited 30 high-risk Tibetan and Han patients with OSAHS, and 30 Tibetan and Han healthy volunteers at the same period. The whole blood viscometer was used to detect the high shear rate of whole blood viscosity, low shear rate of whole blood viscosity, plasma viscosity ratio, red blood cell aggregation index, and hematocrit in each group. RT-qPCR and Western blot assays were used to detect the mRNA and protein levels of phosphoinositide 3-kinase (PI3K), serine/threonine kinase (AKT), nuclear factor-κB (NF-κB) p65, HIF-1α and HIF-2α in peripheral blood mononuclear cells. Results The hemorheology level of Tibetan OSAHS patients was significantly higher than that of healthy Tibetans and Han OSAHS patients (P<0.05), and the hemorheology level of Han OSAHS patients was significantly higher than that of Han healthy people (P<0.05) . The mRNA and protein levels of PI3K, AKT, NF-κB p65 and HIF-1α in the peripheral blood mononuclear cells of Tibetan OSAHS patients were significantly higher than those of the healthy Tibetans or Han people, and these indexes of the Han OSAHS patients were significantly higher than those of the Han healthy people (all P<0.05), while HIF-2α mRNA and protein levels were significantly lower than those of healthy Han people (all P<0.05). Conclusion The upregulation of HIF-1α level and downregulation of HIF-2α expression in peripheral blood mononuclear cells of OSAHS patients depend on the activation of the PI3K/AKT/NF-κB p65 signaling pathway, and the hemorheological level of Tibetan OSAHS patients is higher than that of Han OSAHS patients.

Citation： LA Zhoucuomao, LI Lingyi, GAO Rui, LIU Hong. Differences of hemorheology indexes and expression of HIF-1α/2α in PI3K/Akt/NF-kB p65 signaling pathway between Tibetan and Han OSAHS patients. Chinese Journal of Respiratory and Critical Care Medicine, 2022, 21(7): 471-477. doi: 10.7507/1671-6205.202007070 Copy

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2.	吴天一. 高原低氧环境对人类的挑战. 医学研究杂志, 2006, 35(10): 1-3.
3.	李婧婧. 藏、汉族OSAHS患者血清HIF-2α, EPO、EPOR水平与红细胞、血红蛋白等指标的相关性研究[D]. 青海大学, 2019, 1-38.
4.	Li CY, Liu YY, Xu PF, et al. Association between obstructive sleep apnea and risk of post-stroke depression: a hospital-based study in ischemic stroke patients. J Stroke Cerebrovasc Dis, 2020, 29(8): 104876-104884.
5.	Baguet JP, Hammer L, Leívy P, et al. The severity of oxygen desaturation is predictive of carotid wall thickening and plaque occurrence. Chest, 2005, 128(5): 3407-3412.
6.	Kolluri R, Bashir R, Matros T, et al. Prevalence and predictors of elevated central venous pressure and obstructive sleep apnea in patients with lower extremity chronic venous disease. J Vasc Surg Venous Lymphat Disord, 2020, 8(5): 775-782.
7.	Prabhakar NR, Peng YJ, Nanduri J. Hypoxia-inducible factors and obstructive sleep apnea. J Clin Invest, 2020, 130(10): 5042-5051.
8.	Liu CD, Wang HY, Zhu CB, et al. Plasma expression of HIF-1α as novel biomarker for the diagnosis of obstructive sleep apnea-hypopnea syndrome. J Clin Lab Anal, 2020, 34(12): e23545.
9.	Yu LM, Zhang WH, Han XX, et al. Hypoxia-induced ROS contribute to myoblast pyroptosis during obstructive sleep apnea via the NF-κB/HIF-1α signaling pathway. Oxid Med Cell Longev, 2019, 2019(4): 4596368.
10.	Ram S, Seirawan H, Kumar SK, et al. Prevalence and impact of sleep disorders and sleep habits in the United States. Sleep Breath, 2010, 14(1): 63-70.
11.	朱增民. 红细胞压积对全血黏度关系的影响研究. 当代医学, 2011, 17(29): 20-21.
12.	于丹丹. 阻塞性睡眠呼吸暂停低通气综合征患者血液流变学的变化及其意义. 延边大学, 2017: 1-31.
13.	Toraldo DM, Peverini F, De Benedetto M, et al. Obstructive sleep apnea syndrome: blood viscosity, blood coagulation abnormalities, and early atherosclerosis. Lung, 2013, 191(1): 1-7.
14.	Zhang FJ, Luo W, Lei GH. Role of HIF-1α and HIF-2α in osteoarthritis. Joint Bone Spine, 2015, 82(3): 144-147.
15.	Majmundar AJ, Wong WJ, Simon MC. Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell, 2010, 40(2): 294-309.
16.	Belaidi E, Joyeux-Faure M, Ribuot C, et al. Major role for hypoxia inducible factor-1 and the endothelin system in promoting myocardial infarction and hypertension in an animal model of obstructive sleep apnea. J Am Coll Cardiol, 2009, 53(15): 1309-1317.
17.	Martinez CA, Kerr B, Jin C, et al. Obstructive sleep apnea activates HIF-1 in a hypoxia dose-dependent manner in HCT116 colorectal carcinoma cells. Int J Mol Sci, 2019, 20(2): 445-451.
18.	Abdel-Rahman Mohamed A, M M Metwally M, Khalil SR, et al. Moringa oleifera extract attenuates the CoCl₂ induced hypoxia of rat's brain: expression pattern of HIF-1α, NF-κB, MAO and EPO. Biomed Pharmacother, 2019, 109: 1688-1697.
19.	Bandarra D, Biddlestone J, Mudie S, et al. HIF-1α restricts NF-κB-dependent gene expression to control innate immunity signals. Dis Model Mech, 2015, 8(2): 169-181.
20.	Bonello S, Zähringer C, Belaiba RS, et al. Reactive oxygen species activate the HIF-1α promoter via a functional NFκB site. Arterioscler Thromb Vasc Biol, 2007, 27(4): 755-761.
21.	Iyer NV, Kotch LE, Agani F, et al. Cellular and developmental control of O₂ homeostasis by hypoxia-inducible factor 1α. Genes Dev, 1998, 12(2): 149-162.
22.	Nanduri J, Wang N, Yuan G, et al. Intermittent hypoxia degrades HIF-2α via calpains resulting in oxidative stress: implications for recurrent apnea-induced morbidities. Proc Natl Acad Sci U S A, 2009, 106(4): 1199-1204.
23.	Lam SY, Tipoe GL, Liong EC, et al. Hypoxia-inducible factor (HIF)-1α and endothelin-1 expression in the rat carotid body during intermittent hypoxia. Adv Exp Med Biol, 2006, 580: 21-27.
24.	Nanduri J, Vaddi DR, Khan SA, et al. Xanthine oxidase mediates hypoxia-inducible factor-2α degradation by intermittent hypoxia. PLoS One, 2013, 8(10): e75838.

1. Daurat A, Sarhane M, Tiberge M. Obstructive sleep apnea syndrome and cognition: a review. Neurophysiol Clin, 2016, 46(3): 201-215.
2. 吴天一. 高原低氧环境对人类的挑战. 医学研究杂志, 2006, 35(10): 1-3.
3. 李婧婧. 藏、汉族OSAHS患者血清HIF-2α, EPO、EPOR水平与红细胞、血红蛋白等指标的相关性研究[D]. 青海大学, 2019, 1-38.
4. Li CY, Liu YY, Xu PF, et al. Association between obstructive sleep apnea and risk of post-stroke depression: a hospital-based study in ischemic stroke patients. J Stroke Cerebrovasc Dis, 2020, 29(8): 104876-104884.
5. Baguet JP, Hammer L, Leívy P, et al. The severity of oxygen desaturation is predictive of carotid wall thickening and plaque occurrence. Chest, 2005, 128(5): 3407-3412.
6. Kolluri R, Bashir R, Matros T, et al. Prevalence and predictors of elevated central venous pressure and obstructive sleep apnea in patients with lower extremity chronic venous disease. J Vasc Surg Venous Lymphat Disord, 2020, 8(5): 775-782.
7. Prabhakar NR, Peng YJ, Nanduri J. Hypoxia-inducible factors and obstructive sleep apnea. J Clin Invest, 2020, 130(10): 5042-5051.
8. Liu CD, Wang HY, Zhu CB, et al. Plasma expression of HIF-1α as novel biomarker for the diagnosis of obstructive sleep apnea-hypopnea syndrome. J Clin Lab Anal, 2020, 34(12): e23545.
9. Yu LM, Zhang WH, Han XX, et al. Hypoxia-induced ROS contribute to myoblast pyroptosis during obstructive sleep apnea via the NF-κB/HIF-1α signaling pathway. Oxid Med Cell Longev, 2019, 2019(4): 4596368.
10. Ram S, Seirawan H, Kumar SK, et al. Prevalence and impact of sleep disorders and sleep habits in the United States. Sleep Breath, 2010, 14(1): 63-70.
11. 朱增民. 红细胞压积对全血黏度关系的影响研究. 当代医学, 2011, 17(29): 20-21.
12. 于丹丹. 阻塞性睡眠呼吸暂停低通气综合征患者血液流变学的变化及其意义. 延边大学, 2017: 1-31.
13. Toraldo DM, Peverini F, De Benedetto M, et al. Obstructive sleep apnea syndrome: blood viscosity, blood coagulation abnormalities, and early atherosclerosis. Lung, 2013, 191(1): 1-7.
14. Zhang FJ, Luo W, Lei GH. Role of HIF-1α and HIF-2α in osteoarthritis. Joint Bone Spine, 2015, 82(3): 144-147.
15. Majmundar AJ, Wong WJ, Simon MC. Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell, 2010, 40(2): 294-309.
16. Belaidi E, Joyeux-Faure M, Ribuot C, et al. Major role for hypoxia inducible factor-1 and the endothelin system in promoting myocardial infarction and hypertension in an animal model of obstructive sleep apnea. J Am Coll Cardiol, 2009, 53(15): 1309-1317.
17. Martinez CA, Kerr B, Jin C, et al. Obstructive sleep apnea activates HIF-1 in a hypoxia dose-dependent manner in HCT116 colorectal carcinoma cells. Int J Mol Sci, 2019, 20(2): 445-451.
18. Abdel-Rahman Mohamed A, M M Metwally M, Khalil SR, et al. Moringa oleifera extract attenuates the CoCl₂ induced hypoxia of rat's brain: expression pattern of HIF-1α, NF-κB, MAO and EPO. Biomed Pharmacother, 2019, 109: 1688-1697.
19. Bandarra D, Biddlestone J, Mudie S, et al. HIF-1α restricts NF-κB-dependent gene expression to control innate immunity signals. Dis Model Mech, 2015, 8(2): 169-181.
20. Bonello S, Zähringer C, Belaiba RS, et al. Reactive oxygen species activate the HIF-1α promoter via a functional NFκB site. Arterioscler Thromb Vasc Biol, 2007, 27(4): 755-761.
21. Iyer NV, Kotch LE, Agani F, et al. Cellular and developmental control of O₂ homeostasis by hypoxia-inducible factor 1α. Genes Dev, 1998, 12(2): 149-162.
22. Nanduri J, Wang N, Yuan G, et al. Intermittent hypoxia degrades HIF-2α via calpains resulting in oxidative stress: implications for recurrent apnea-induced morbidities. Proc Natl Acad Sci U S A, 2009, 106(4): 1199-1204.
23. Lam SY, Tipoe GL, Liong EC, et al. Hypoxia-inducible factor (HIF)-1α and endothelin-1 expression in the rat carotid body during intermittent hypoxia. Adv Exp Med Biol, 2006, 580: 21-27.
24. Nanduri J, Vaddi DR, Khan SA, et al. Xanthine oxidase mediates hypoxia-inducible factor-2α degradation by intermittent hypoxia. PLoS One, 2013, 8(10): e75838.

Chinese Journal of Respiratory and Critical Care Medicine

Differences of hemorheology indexes and expression of HIF-1α/2α in PI3K/Akt/NF-kB p65 signaling pathway between Tibetan and Han OSAHS patients

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