Study on the serum miRNA-92a level and vascular endothelial function injury in OSAHS patients_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

 SHANG Fenqing ¹ , GUO Xuan ¹ , GU Xing ²

1. Department of Cardiology, Xi'an First Hospital, Xi'an, Shaanxi 710002, P. R. China;
2. Department of Respiratory Medicine, Xi'an Chest Hospital, Xi'an, Shaanxi 710000, P. R. China;

Corresponding?author：

SHANG Fenqing, Email: shangfenqing@163.com

Keywords：

Obstuctive sleep apnoea hypopnea syndrome; miRNA-92a; Endothelial cells

DOI：

10.7507/1671-6205.202009043

Video：

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Objective To clarify that the vascular endothelial cell injury caused by obstructive sleep apnoea hypopnea syndrome (OSAHS) is partly mediated by miRNA-92a. Methods Serum miRNA-92a level was measured in patients who underwent polysomnography between January 2018 and December 2018. The correlation between miRNA-92a and OSAHS was analyzed. Meanwhile, endothelial cells were cultured in vitro, and morphological changes and JC-1 staining results of endothelial cells were observed after OSAHS serum stimulation, so as to further clarify the injury of endothelial cells. The changes of miRNA-92a target gene were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot to further clarify the mechanism of endothelial cell injury. Results Seventy-two patients received polysomnography, including 22 cases in the non-OSAHS group, 18 in the mild OSAHS group, 10 in the moderate OSAHS group, and 22 in the severe OSAHS group. Serum miRNA-92a level was significantly increased in the OSAHS patients, and it also increased with the aggravation of OSAHS severity. OSAHS serum significantly damaged endothelial cells. Endothelial cells were swollen, disordered arrangement, and unclear boundaries. JC-1 staining showed that green fluorescence was significantly enhanced compared with the control group. RT-PCR and Western blot showed that the expressions of Krüppel-like factor-2 (KLF-2), Krüppel-like factor-4 (KLF-4) and endothelial nitric oxide synthase (eNOS) were significantly decreased under OSAHS serum stimulation. Conclusion Serum miRNA-92a of OSAHS patients is significantly increased, and reduces the expression of target genes KLF-2, KLF-4 and eNOS, affects the mitochondrial function of endothelial cells, and injures endothelial cells.

Citation： SHANG Fenqing, GUO Xuan, GU Xing. Study on the serum miRNA-92a level and vascular endothelial function injury in OSAHS patients. Chinese Journal of Respiratory and Critical Care Medicine, 2021, 20(9): 625-631. doi: 10.7507/1671-6205.202009043 Copy

1.	Voulgaris A, Archontogeorgis K, Papanas N, et al. Increased risk for cardiovascular disease in patients with obstructive sleep apnoea syndrome-chronic obstructive pulmonary disease (overlap syndrome). Clin Respir J, 2019, 13(11): 708-715.
2.	葉玉蘭, 尚粉青, 李齊斐, 等. 高血壓患者血清 microRNA-92a 水平與大動脈僵硬度的關系. 中國分子心臟病學雜志, 2018, 18(3): 2457-2461.
3.	Chen Z, Wen L, Martin M, et al. Oxidative stress activates endothelial innate immunity via sterol regulatory element binding protein 2 (SREBP2) transactivation of microRNA-92a. Circulation, 2015, 131(9): 805-814.
4.	Bonauer A, Carmona G, Wasaki M, et al. MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science, 2009, 324(5935): 1710-1713.
5.	Kapur VK, Auckley DH, Chowdhuri S, et al. Clinical Practice Guideline for Diagnostic Testing for Adult Obstructive Sleep Apnea: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med, 2017, 13(3): 479-504.
6.	尚粉青, 嚴龍龍, 張玎, 等. 高糖通過調節腺苷酸活化蛋白激酶/聚二磷酸腺苷核糖聚合酶-1 的磷酸化抑制 B 細胞/血友病-6 基因表達的研究. 中國糖尿病雜志, 2016, 24(11): 1003-1006.
7.	Guilleminault C, Eldridge F, Simmons F, et al. Sleep apnea in eight children. Pediatrics, 1976, 58(1): 23-30.
8.	Balk EM, Moorthy D, Obadan NO, et al. Diagnosis and treatment of obstructive sleep apnea in adults: comparative effectiveness review No. 32. Rockville, MD: Agency for Healthcare Research and Quality, 2011 Jul. Report No. : 11-EHC052.
9.	中華醫學會呼吸病學分會睡眠呼吸疾病學組. 睡眠呼吸暫停人群高血壓患病率的多中心研究. 中華結核和呼吸雜志, 2007, 30(12): 894-897.
10.	McNicholas WT, Bonsigore MR; Management Committee of EU COST ACTION B26. Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities. Eur Respir J, 2007, 29(1): 156-178.
11.	Webster BR, Osmond JM, Paredes DA, et al. Phosphoinositide-dependent kinase-1 and protein kinase Cδ contribute to endothelin-1 constriction and elevated blood pressure in intermittent hypoxia. J Pharmacol Exp Ther, 2013, 344(1): 68-76.
12.	Gautier-Veyret E, Van Noolen L, Lévy P, et al. Could the thromboxane A2 pathway be a therapeutic target for the treatment of obstructive sleep apnea-induced atherosclerosis?. Prostaglandins Other Lipid Mediat, 2015, 121(PtA): 97-104.
13.	陳云霞, 陳寶元, 曹潔, 等. 不同間歇低氧暴露內皮細胞與多形核白細胞共培養下核轉錄因子 KBp65 表達水平的研究. 中國呼吸與危重監護雜志, 2014, 13(2): 150-153.
14.	Wu W, Xiao H, Laguna-Fernandez A, et al. Flow-dependent regulation of Krüppel-like factor 2 is mediated by microRNA-92a. Circulation, 2011, 124(5): 633-641.
15.	王虹, 林忠英, 陸紅梅, 等. ST 段抬高型心肌梗死患者循環微 RNA-92a 表達的研究. 中國危重病急救雜志, 2011, 23(12): 718-722.
16.	王虹, 林英忠, 周瑩, 等. 老年穩定性心絞痛患者循環微 RNA-92a 表達的影響因素研究. 中華老年心腦血管病雜志, 2012, 14(4): 364-366.
17.	趙婷婷, 尚粉青, 郭娟英, 等. 阿托伐他汀降低慢性腎病患者血清及腎臟 microRNA-92a 的表達. 實用醫藥雜志, 2019, 12(12): 1107-1110.
18.	Liu HX, Li GF, Zhao WX, et al. Inhibition of MiRNA-92a may protect endothelial cells after acute myocardial infarction in rats: role of KLF2/4. Med Sci Monit, 2016, 14(22): 2451-2462.
19.	Shang FQ, Wang SC, Hsu CY, et al. MicroRNA-92a mediates endothelial dysfunction in chronic kidney disease. J Am Soc Nephrol, 2017, 28(11): 3250-3260.
20.	Khalyfa A, Kheirandish-gozal L, Khalyfa A, et al. Circulating plasma extracellular microvesicle MicroRNA cargo and endothelial dysfunctionin children with obstructive sleep apnea. Am J Respir Crit Care Med, 2016, 194(9): 1116-1126.
21.	Bi RR, Dai YC, Ma ZF, et al. Endothelial cell autophagy in chronic intermittent hypoxia is impaired by miRNA-30a-mediated translational control of Beclin-1. J Cell Biochem, 2019, 120(3): 4214-4224.
22.	Zhu J, Kang J, Li XC, et al. Chronic intermittent hypoxia vs chronic continuous hypoxia: effects on vascular endothelial function and myocardial contractility. Clin Hemorheol Microcirc, 2020, 74(4): 417-427.
23.	Haslip M, Dostanic I, Huang Y, et al. Endothelial uncoupling protein 2 regulates mitophagy and pulmonary hypertension during intermittent hypoxia. Arterioscler Thromb Vasc Biol, 2015, 35(5): 1166-1178.

1. Voulgaris A, Archontogeorgis K, Papanas N, et al. Increased risk for cardiovascular disease in patients with obstructive sleep apnoea syndrome-chronic obstructive pulmonary disease (overlap syndrome). Clin Respir J, 2019, 13(11): 708-715.
2. 葉玉蘭, 尚粉青, 李齊斐, 等. 高血壓患者血清 microRNA-92a 水平與大動脈僵硬度的關系. 中國分子心臟病學雜志, 2018, 18(3): 2457-2461.
3. Chen Z, Wen L, Martin M, et al. Oxidative stress activates endothelial innate immunity via sterol regulatory element binding protein 2 (SREBP2) transactivation of microRNA-92a. Circulation, 2015, 131(9): 805-814.
4. Bonauer A, Carmona G, Wasaki M, et al. MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science, 2009, 324(5935): 1710-1713.
5. Kapur VK, Auckley DH, Chowdhuri S, et al. Clinical Practice Guideline for Diagnostic Testing for Adult Obstructive Sleep Apnea: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med, 2017, 13(3): 479-504.
6. 尚粉青, 嚴龍龍, 張玎, 等. 高糖通過調節腺苷酸活化蛋白激酶/聚二磷酸腺苷核糖聚合酶-1 的磷酸化抑制 B 細胞/血友病-6 基因表達的研究. 中國糖尿病雜志, 2016, 24(11): 1003-1006.
7. Guilleminault C, Eldridge F, Simmons F, et al. Sleep apnea in eight children. Pediatrics, 1976, 58(1): 23-30.
8. Balk EM, Moorthy D, Obadan NO, et al. Diagnosis and treatment of obstructive sleep apnea in adults: comparative effectiveness review No. 32. Rockville, MD: Agency for Healthcare Research and Quality, 2011 Jul. Report No. : 11-EHC052.
9. 中華醫學會呼吸病學分會睡眠呼吸疾病學組. 睡眠呼吸暫停人群高血壓患病率的多中心研究. 中華結核和呼吸雜志, 2007, 30(12): 894-897.
10. McNicholas WT, Bonsigore MR; Management Committee of EU COST ACTION B26. Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities. Eur Respir J, 2007, 29(1): 156-178.
11. Webster BR, Osmond JM, Paredes DA, et al. Phosphoinositide-dependent kinase-1 and protein kinase Cδ contribute to endothelin-1 constriction and elevated blood pressure in intermittent hypoxia. J Pharmacol Exp Ther, 2013, 344(1): 68-76.
12. Gautier-Veyret E, Van Noolen L, Lévy P, et al. Could the thromboxane A2 pathway be a therapeutic target for the treatment of obstructive sleep apnea-induced atherosclerosis?. Prostaglandins Other Lipid Mediat, 2015, 121(PtA): 97-104.
13. 陳云霞, 陳寶元, 曹潔, 等. 不同間歇低氧暴露內皮細胞與多形核白細胞共培養下核轉錄因子 KBp65 表達水平的研究. 中國呼吸與危重監護雜志, 2014, 13(2): 150-153.
14. Wu W, Xiao H, Laguna-Fernandez A, et al. Flow-dependent regulation of Krüppel-like factor 2 is mediated by microRNA-92a. Circulation, 2011, 124(5): 633-641.
15. 王虹, 林忠英, 陸紅梅, 等. ST 段抬高型心肌梗死患者循環微 RNA-92a 表達的研究. 中國危重病急救雜志, 2011, 23(12): 718-722.
16. 王虹, 林英忠, 周瑩, 等. 老年穩定性心絞痛患者循環微 RNA-92a 表達的影響因素研究. 中華老年心腦血管病雜志, 2012, 14(4): 364-366.
17. 趙婷婷, 尚粉青, 郭娟英, 等. 阿托伐他汀降低慢性腎病患者血清及腎臟 microRNA-92a 的表達. 實用醫藥雜志, 2019, 12(12): 1107-1110.
18. Liu HX, Li GF, Zhao WX, et al. Inhibition of MiRNA-92a may protect endothelial cells after acute myocardial infarction in rats: role of KLF2/4. Med Sci Monit, 2016, 14(22): 2451-2462.
19. Shang FQ, Wang SC, Hsu CY, et al. MicroRNA-92a mediates endothelial dysfunction in chronic kidney disease. J Am Soc Nephrol, 2017, 28(11): 3250-3260.
20. Khalyfa A, Kheirandish-gozal L, Khalyfa A, et al. Circulating plasma extracellular microvesicle MicroRNA cargo and endothelial dysfunctionin children with obstructive sleep apnea. Am J Respir Crit Care Med, 2016, 194(9): 1116-1126.
21. Bi RR, Dai YC, Ma ZF, et al. Endothelial cell autophagy in chronic intermittent hypoxia is impaired by miRNA-30a-mediated translational control of Beclin-1. J Cell Biochem, 2019, 120(3): 4214-4224.
22. Zhu J, Kang J, Li XC, et al. Chronic intermittent hypoxia vs chronic continuous hypoxia: effects on vascular endothelial function and myocardial contractility. Clin Hemorheol Microcirc, 2020, 74(4): 417-427.
23. Haslip M, Dostanic I, Huang Y, et al. Endothelial uncoupling protein 2 regulates mitophagy and pulmonary hypertension during intermittent hypoxia. Arterioscler Thromb Vasc Biol, 2015, 35(5): 1166-1178.

Chinese Journal of Respiratory and Critical Care Medicine

Study on the serum miRNA-92a level and vascular endothelial function injury in OSAHS patients

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