Yan Xu1,2, Tao Hu2, Huizhen Ding2, Yi Yuan3, Rui Chen4. 1. Department of Respiratory, The Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Road, Jiangsu, 215004, Suzhou, China. 2. Department of Respiratory, The Affiliated Hospital of Yangzhou University, No. 45 Taizhou Road, Jiangsu, 225001, Yangzhou, China. 3. Institute of Life Sciences, Jiangsu University, No. 301 Xuefu Road, Jiangsu, 212013, Zhenjiang , China. 4. Department of Respiratory, The Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Road, Jiangsu, 215004, Suzhou, China. chenrui_good@sina.com.
Abstract
OBJECTIVE: The obstructive sleep apnea syndrome (OSAS) is a risk factor for hypertension. MiRNAs are key regulators in hypertension. However, their roles in OSAS with hypertension remain unclear. This study aimed to clarify the function and mechanism of miRNAs in OSAS with hypertension. METHODS: A chronic intermittent hypoxia (CIH) model was established to simulate OSAS with hypertension. The proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) were assessed by CCK-8 and wound healing assays. qRT-PCR, Western blot, and immunofluorescence staining were used to detect the expression of HIF3A and PI3K/AKT pathway. Hematoxylin-eosin and Masson staining were used to detect the histopathological changes of pulmonary arterial hypertension (PAH). The regulatory function of miR-485-5p to HIF3A was assessed by dual luciferase reporter gene assay. RESULTS: MiR-485-5p was significantly downregulated in the rats with OSAS-induced PAH. MiR-485-5p alleviated proliferation and migration of PASMCs in vitro and ameliorated OSAS-induced PAH in vivo. HIF3A could act as a target of miR-485-5p. HIF3A downregulation regulated by miR-485-5p alleviated proliferation and migration of PASMCs in vitro and ameliorated OSAS-induced PAH in vivo. In addition, we found that PI3K/AKT signaling was significantly inhibited in OSAS-induced PAH. CONCLUSION: MiR-485-5p alleviates OSAS with hypertension by inhibiting the PI3K/Akt pathway via downregulating HIF3A expression through the PI3K/AKT pathway. These findings suggest that miR-485-5p has the potential for treating OSAS-associated hypertension.
OBJECTIVE: The obstructive sleep apnea syndrome (OSAS) is a risk factor for hypertension. MiRNAs are key regulators in hypertension. However, their roles in OSAS with hypertension remain unclear. This study aimed to clarify the function and mechanism of miRNAs in OSAS with hypertension. METHODS: A chronic intermittent hypoxia (CIH) model was established to simulate OSAS with hypertension. The proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) were assessed by CCK-8 and wound healing assays. qRT-PCR, Western blot, and immunofluorescence staining were used to detect the expression of HIF3A and PI3K/AKT pathway. Hematoxylin-eosin and Masson staining were used to detect the histopathological changes of pulmonary arterial hypertension (PAH). The regulatory function of miR-485-5p to HIF3A was assessed by dual luciferase reporter gene assay. RESULTS: MiR-485-5p was significantly downregulated in the rats with OSAS-induced PAH. MiR-485-5p alleviated proliferation and migration of PASMCs in vitro and ameliorated OSAS-induced PAH in vivo. HIF3A could act as a target of miR-485-5p. HIF3A downregulation regulated by miR-485-5p alleviated proliferation and migration of PASMCs in vitro and ameliorated OSAS-induced PAH in vivo. In addition, we found that PI3K/AKT signaling was significantly inhibited in OSAS-induced PAH. CONCLUSION: MiR-485-5p alleviates OSAS with hypertension by inhibiting the PI3K/Akt pathway via downregulating HIF3A expression through the PI3K/AKT pathway. These findings suggest that miR-485-5p has the potential for treating OSAS-associated hypertension.