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Mirabegron Ameliorated Atherosclerosis of ApoE-/- Mice in Chronic Intermittent Hypoxia but Not in Normoxia.
Wang, Yue; Wang, Yue; Jiang, Hong-Feng; Dang, Hai-Ming; Liu, Meng-Ru; Liu, Xin-Yan; Yu, Yang; Xie, Jiang; Zhan, Xiao-Jun; Zhang, Hui-Na; Wu, Xiao-Fan.
Afiliación
  • Wang Y; Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
  • Wang Y; Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
  • Jiang HF; Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Collaborative Innovation Center for Cardiovascular Disorders, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
  • Dang HM; Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
  • Liu MR; Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
  • Liu XY; Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
  • Yu Y; Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
  • Xie J; Department of Respiratory and Critical Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
  • Zhan XJ; Sleep Medicine Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
  • Zhang HN; Key Laboratory of Upper Airway Dysfunction-Related Cardiovascular Diseases, Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
  • Wu XF; Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China. drwuxf@163.com.
Cardiovasc Drugs Ther ; 36(5): 805-815, 2022 10.
Article en En | MEDLINE | ID: mdl-34152510
PURPOSE: It has been established that obstructive sleep apnea (OSA) is an independent risk factor for atherosclerosis. Chronic intermittent hypoxia (CIH) activates sympathoadrenal system and upregulates ß3 adrenergic receptor (ß3 AR). However, the effect of selective ß3 AR agonist mirabegron in CIH-induced atherosclerosis remains unknown. METHODS: We generated a CIH-induced atherosclerosis model through exposing ApoE-/- mice to CIH (8 h per day, cyclic inspiratory oxygen fraction 5-21%, 60-s cycle) for 6 weeks after 4-week high-fat dieting and investigated the effects of mirabegron, a selective ß3 AR agonist, on CIH-induced atherosclerosis. The coronary endarterectomy (CE) specimens from coronary artery disease patients with OSA and without OSA were collected. RESULTS: The expression of ß3 AR was significantly elevated in CIH-induced atherosclerosis model. Furthermore, treatment with mirabegron (10mg/kg per day by oral administration for 6 weeks) ameliorated atherosclerosis in ApoE-/- mice in CIH but not in normoxia. Mechanistically, mirabegron activated ß3 AR and ameliorated intraplaque oxidative stress by suppressing p22phox expression and reactive oxygen species (ROS) level. In addition, in human CE specimens, ß3 AR was also upregulated associated with increased p22phox expression and ROS level both in the lumen and in the plaque of coronary artery in OSA subjects. CONCLUSION: This study first demonstrated that mirabegron impeded the progression of CIH-induced atherosclerosis, at least in part, via ß3 AR-mediated oxidative stress, suggesting a promising therapeutic strategy for protecting against atherosclerosis induced by CIH.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Apnea Obstructiva del Sueño / Aterosclerosis Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Cardiovasc Drugs Ther Asunto de la revista: ANGIOLOGIA / CARDIOLOGIA / TERAPIA POR MEDICAMENTOS Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Apnea Obstructiva del Sueño / Aterosclerosis Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Cardiovasc Drugs Ther Asunto de la revista: ANGIOLOGIA / CARDIOLOGIA / TERAPIA POR MEDICAMENTOS Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos