Qiu Xuan, Yao Yanli, Chen Yulan, Li Yu, Sun Xiaojing, Zhu Xiaoli
Department of Hypertension, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, People's Republic of China.
Second Department of Comprehensive Internal Medicine of Healthy Care Center for Cadres, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, People's Republic of China.
Nat Sci Sleep. 2024 Dec 19;16:2125-2141. doi: 10.2147/NSS.S494748. eCollection 2024.
Intermittent hypoxia (IH), a defining feature of obstructive sleep apnea (OSA), is associated with heart damage and linked to transient receptor potential canonical channel 5 (TRPC5). Nonetheless, the function of TRPC5 in OSA-induced cardiac injury remains uncertain. For this research, we aimed to explore the role and potential mechanism of TRPC5 in cardiomyocyte injury induced by intermittent hypoxia.
30 patients with newly diagnosed OSA and 30 patients with primary snoring(PS) were included in this study. Participants were subjected to polysomnography (PSG) for OSA diagnosis. Echocardiography was used to evaluate the structure and function of the heart, while peripheral blood samples were obtained. Additionally, RT-qPCR was utilized to quantify the relative expression level of TRPC5 mRNA in peripheral blood. H9c2 cells experienced IH or normoxia. TRPC5 levels in H9c2 cells were determined via RT-qPCR and Western blotting (WB) methods. H9c2 cells overexpressing TRPC5 were subjected to either normoxic or intermittent hypoxia conditions. Cell viability was determined by CCK8, the apoptosis rate, reactive oxygen species(ROS) levels, and Ca concentration were assessed by flow cytometry, and the protein levels of TRPC5, Bcl-2, Bax, and Caspase-3 were analyzed by WB. Mitochondrial membrane potential(MMP), mitochondrial membrane permeability transition pore(mPTP), and transmission electron microscopy(TEM) were employed to observe mitochondrial function and structure. After inhibiting ROS with N-acetylcysteine (NAC), apoptosis, mitochondrial function and structure, and the concentration of Ca were further detected.
TRPC5 and left atrial diameter (LAD) were higher in OSA individuals, while the E/A ratio was lower(all <0.05). IH impaired cell viability, triggered cell apoptosis, and enhanced TRPC5 expression in H9c2 cells(all <0.05). The effects of IH on apoptosis, cell viability, mitochondrial function and structure damage, and oxidative stress (OxS) in H9c2 cells were accelerated by the overexpression of TRPC5(all <0.05). Furthermore, cell apoptosis and mitochondrial structural and functional damage caused by overexpression of TRPC5 were attenuated by ROS inhibition.
TRPC5 is associated with structural and functional cardiac damage in patients with OSA, and TRPC5 promotes IH-induced apoptosis and mitochondrial damage in cardiomyocytes through OxS. TRPC5 may be a novel target for the diagnosis and treatment of OSA-induced myocardial injury.
间歇性缺氧（IH）是阻塞性睡眠呼吸暂停（OSA）的一个典型特征，与心脏损伤相关，并与瞬时受体电位香草酸受体5（TRPC5）有关。然而，TRPC5在OSA诱导的心脏损伤中的作用仍不确定。在本研究中，我们旨在探讨TRPC5在间歇性缺氧诱导的心肌细胞损伤中的作用及潜在机制。
本研究纳入30例新诊断的OSA患者和30例原发性打鼾（PS）患者。参与者接受多导睡眠图（PSG）检查以诊断OSA。使用超声心动图评估心脏的结构和功能，同时采集外周血样本。此外，采用逆转录-定量聚合酶链反应（RT-qPCR）定量外周血中TRPC5 mRNA的相对表达水平。H9c2细胞经历间歇性缺氧或常氧处理。通过RT-qPCR和蛋白质免疫印迹法（WB）测定H9c2细胞中TRPC5的水平。过表达TRPC5的H9c2细胞分别置于常氧或间歇性缺氧条件下。通过CCK8法测定细胞活力，通过流式细胞术评估凋亡率、活性氧（ROS）水平和钙离子浓度，通过WB分析TRPC5、Bcl-2、Bax和Caspase-3的蛋白水平。采用线粒体膜电位（MMP）、线粒体膜通透性转换孔（mPTP）和透射电子显微镜（TEM）观察线粒体功能和结构。用N-乙酰半胱氨酸（NAC）抑制ROS后，进一步检测细胞凋亡、线粒体功能和结构以及钙离子浓度。
OSA患者的TRPC5和左心房内径（LAD）较高，而E/A比值较低（均<0.05）。间歇性缺氧损害H9c2细胞的活力，引发细胞凋亡，并增强TRPC5的表达（均<0.05）。TRPC5过表达加速了间歇性缺氧对H9c2细胞凋亡、细胞活力、线粒体功能和结构损伤以及氧化应激（OxS）的影响（均<0.05）。此外，ROS抑制减弱了TRPC5过表达引起的细胞凋亡以及线粒体结构和功能损伤。
TRPC5与OSA患者的心脏结构和功能损伤相关，并且TRPC5通过氧化应激促进间歇性缺氧诱导的心肌细胞凋亡和线粒体损伤。TRPC5可能是OSA诱导的心肌损伤诊断和治疗的新靶点。
