Department of Geriatrics, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, China.
Department of Cardiovascular Internal Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014.
Cell Mol Biol (Noisy-le-grand). 2022 Jan 2;67(4):91-96. doi: 10.14715/cmb/2021.67.4.10.
Hypertension occurred in 50% obstructive sleep apnea-hypopnea syndrome (OSAHS) patients meanwhile OSAHS occurred in 30% hypertension patients. The present study aimed to explore the molecular mechanism of GATA2-EDN1-AGT induced hypertension in the development of obstructive sleep apnea-hypopnea syndrome. OSAHS patients (56 cases: 36 cases of male, 20 cases of female, 42~60 years old) were divided into two groups (case group: patients with hypertension monitored by 24 h ambulatory blood pressure and polysomnography; control group: patients without hypertension). Wistar rats were used to establish the OSAHS model (narrow pharyngeal cavity). PaO2 and PaCO2 of patients and rats were measured by an automatic blood gas analyzer. The profile of total protein in the OSAHS group and normal group was evaluated. Protein-protein-interaction (PPI) was carried out to show all matter proteins related. The levels of EDN-1, AGTII and atrial natriuretic peptide (ANP) in blood samples of patients and rats were analyzed by enzyme-linked immunosorbent assay (ELISA). The expression of GATA2, EDN1, endothelin-converting enzyme 1 (ECE-1) and AGTⅡ was measured. The results showed that SaO2 and AHI were positively associated with systolic pressure (P<0.05) in OSAHS patients. There was no correlation among other indexes (P>0.05). It was also observed that GATA2 had a strong relationship with AGTⅡ and EDN1. The results of ELISA presented that the levels of EDN1, AGTⅡ and ANP in the OSAHS group of human and animal models were significantly increased (P<0.05). The results of immunochemistry showed that the expression of GATA2 and AGTⅡ in the vascular of OSAHS group was upregulated manifestly (P<0.05). It was concluded that OSAHS can induce AHI, which increases hypertension via the GATA2-EDN1-AGT Ⅱ axis.
高血压发生于 50%阻塞性睡眠呼吸暂停低通气综合征（OSAHS）患者，同时 OSAHS 发生于 30%高血压患者中。本研究旨在探讨 GATA2-EDN1-AGT 诱导的高血压在阻塞性睡眠呼吸暂停低通气综合征发展中的分子机制。OSAHS 患者（56 例：男 36 例，女 20 例，42~60 岁）分为两组（病例组：通过 24 小时动态血压监测和多导睡眠图监测的高血压患者；对照组：无高血压患者）。使用 Wistar 大鼠建立 OSAHS 模型（狭窄咽腔）。通过自动血气分析仪测量患者和大鼠的 PaO2 和 PaCO2。评估 OSAHS 组和正常组的总蛋白图谱。进行蛋白质-蛋白质相互作用（PPI）以显示所有相关物质蛋白。通过酶联免疫吸附测定（ELISA）分析患者和大鼠血液样本中 EDN-1、AGTII 和心房利钠肽（ANP）的水平。测量 GATA2、EDN1、内皮素转换酶 1（ECE-1）和 AGTII 的表达。结果表明，SaO2 和 AHI 与收缩压呈正相关（P<0.05）。其他指标之间没有相关性（P>0.05）。还观察到 GATA2 与 AGTII 和 EDN1 具有很强的关系。ELISA 结果显示，人及动物模型 OSAHS 组的 EDN1、AGTII 和 ANP 水平显著升高（P<0.05）。免疫化学结果显示，OSAHS 组血管中 GATA2 和 AGTII 的表达明显上调（P<0.05）。结论：OSAHS 可导致 AHI，通过 GATA2-EDN1-AGT Ⅱ轴增加高血压的发生。
