Obstructive sleep apnea–hypopnea syndrome (OSAHS) is a common sleep disorder marked by repeated episodes of complete or partial upper-airway obstruction during sleep [1]. This condition results in repetitive breathing pauses and hypopnea, leading to a range of nocturnal and diurnal symptoms, including snoring, nocturnal awakenings, and daytime sleepiness [2]. Globally, the incidence of OSAHS is rising, positioning it as a significant public health concern [3,4]. Studies have linked OSAHS with an increased risk of various cardiovascular diseases, such as hypertension, coronary artery disease, arrhythmias, and even sudden cardiac death [5,6]. This association is primarily due to endothelial dysfunction induced by OSAHS, as endothelial cells are critical in maintaining the structural and functional integrity of blood vessels [7]. Endothelial dysfunction is an early biomarker of cardiovascular disease and is closely associated with atherosclerosis and subsequent cardiovascular events [8]. The health of endothelial cells is essential for the normal functioning of blood vessels, and damage to these cells caused by OSAHS can lead to vascular inflammation and atherosclerotic changes. Therefore, exploring the mechanisms linking OSAHS with endothelial dysfunction is crucial for developing new therapeutic strategies [9].

Calcium ion (Ca2+) signaling is a key second messenger for endothelial cells to maintain vascular tone, barrier function, and inflammatory response homeostasis; abnormal Ca2+ influx can drive oxidative stress and inflammation amplification, thereby accelerating vascular pathological processes associated with endothelial dysfunction. The transient receptor potential (TRP) channel family is an important source of Ca2+ channels and has been confirmed to be widely expressed in vascular endothelial cells and involved in vascular function regulation [10]. Among them, TRPC5, as a Ca2+-permeable non-selective cation channel, has distinct functional significance in vascular endothelial cells, participating in endothelium-dependent vascular responses and correlating with endothelial dysfunction [11]. Previous studies also suggest that TRPC5 can be associated with processes such as oxidative stress/endothelial senescence, thereby affecting vascular homeostasis and the progression of vascular injury [12,13]. Therefore, targeting TRPC5 to inhibit abnormal Ca2+ influx may provide a new point of intervention for improving OSAHS-related vascular endothelial dysfunction.

Current treatments for OSAHS primarily focus on continuous positive airway pressure (CPAP) and upper airway surgical interventions [14]. Although these methods are effective in reducing apneic episodes and snoring frequency, their efficacy in addressing the vascular dysfunction caused by OSAHS remains unclear [6]. Additionally, poor patient compliance with CPAP limits its widespread clinical use [15]. Recently, stem cell therapy has attracted growing clinical interest due to its regenerative and immunomodulatory capabilities. Stem cells possess unique self-renewal and multilineage differentiation abilities, demonstrating significant potential across various medical fields [16]. Mesenchymal stem cells (MSCs) are adult stem cells present in most postnatal tissues and maintain tissue homeostasis through strong regenerative, pro-angiogenic, and immunomodulatory effects. The chronic intermittent hypoxia, oxidative stress, and inflammatory environment induced by OSAHS can recruit MSCs from tissue niches; through their secretion of anti-inflammatory and pro-angiogenic factors, MSCs can alleviate hypoxic injury, inhibit inflammation, and prevent fibrosis, thereby promoting the regeneration of damaged cells [17]. These EVs, rich in bioactive molecules, can repair damaged tissues and modulate immune responses without the direct use of live cells, thereby reducing potential immunogenic rejections and other risks [18]. However, improving EV targeting and therapeutic efficacy, and achieving precise, disease-specific control of their functions, remain major challenges in current research [19].

The objective of this study is to improve OSAHS-associated endothelial dysfunction by using ICAM-1+H-EVs to inhibit the TRPC5 channel and reduce calcium influx. Given that TRPC5-mediated Ca2+ influx is associated with endothelial dysfunction and vascular pathological processes, we further explore the mechanistic significance of TRPC5 as an intervention target in OSAHS-related vascular injury. We aim to confirm the effectiveness of this therapeutic strategy in animal models and to establish a theoretical foundation for clinical translation. This work advances understanding of the link between OSAHS and vascular dysfunction and may clarify how calcium regulation in endothelial cells contributes to vascular homeostasis. If validated in clinical trials, this approach could provide a new option for OSAHS patients, especially those with poor responses to conventional treatments. Moreover, these findings may inform therapeutic strategies for other cardiovascular diseases and offer fresh insight into comprehensive cardiovascular management.