TRPC5 Promotes Intermittent Hypoxia-Induced Cardiomyocyte Injury Through Oxidative Stress.

Abstract

Purpose: 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.

Methods: 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 Ca²⁺ 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 Ca²⁺ were further detected.

Results: TRPC5 and left atrial diameter (LAD) were higher in OSA individuals, while the E/A ratio was lower(all P<0.05). IH impaired cell viability, triggered cell apoptosis, and enhanced TRPC5 expression in H9c2 cells(all P<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 P<0.05). Furthermore, cell apoptosis and mitochondrial structural and functional damage caused by overexpression of TRPC5 were attenuated by ROS inhibition.

Conclusion: 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.