Spermine on Endothelial Extracellular Vesicles Mediates Smoking-Induced Pulmonary Hypertension Partially Through Calcium-Sensing Receptor

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 39; no. 3; pp. 482 - 495
• Main Authors: Zhu, Liping, Xiao, Rui, Zhang, Xiuyun, Lang, Yuheng, Liu, Fangbo, Yu, Zhe, Zhang, Jiwei, Su, Yuan, Lu, Yankai, Wang, Tao, Luo, Shengquan, Wang, Jian, Liu, Ming-Lin, Dupuis, Jocelyn, Jing, Zhi-Cheng, Li, Tong, Xiong, Weining, Hu, Qinghua
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.03.2019
• Subjects: Animals; Benzamides - pharmacology; Biological Transport; Calcium - physiology; Calcium Signaling - drug effects; Calcium Signaling - physiology; Cyclohexylamines - pharmacology; Endothelial Cells - metabolism; Endothelium, Vascular - metabolism; Extracellular Vesicles - chemistry; Extracellular Vesicles - physiology; Gene Knockdown Techniques; Hypertension, Pulmonary - etiology; Hypertension, Pulmonary - physiopathology; Hypertension, Pulmonary - prevention & control; Male; Myocytes, Smooth Muscle - metabolism; Pulmonary Artery - drug effects; Pulmonary Artery - metabolism; Pulmonary Artery - pathology; Random Allocation; Rats; Rats, Sprague-Dawley; Receptors, Calcium-Sensing - antagonists & inhibitors; Receptors, Calcium-Sensing - deficiency; Receptors, Calcium-Sensing - genetics; Receptors, Calcium-Sensing - physiology; RNA Interference; RNA, Small Interfering - genetics; RNA, Small Interfering - pharmacology; Spermine - biosynthesis; Spermine - physiology; Tobacco Smoke Pollution - adverse effects; Tobacco Smoking - adverse effects; endothelium; calcium-sensing receptor; spermine; pulmonary hypertension; smoking

OBJECTIVE—This study aims to determine whether and how the enriched metabolites of endothelial extracellular vesicles (eEVs) are critical for cigarette smoke-induced direct injury of endothelial cells and the development of pulmonary hypertension, rarely explored in contrast to long-investigated mec...