PMID- 28117274 OWN - NLM STAT- MEDLINE DCOM- 20180222 LR - 20181024 IS - 1878-7436 (Electronic) IS - 1878-7436 (Linking) VI - 11 IP - 3 DP - 2017 Mar TI - Schisandrin B displays a protective role against primary pulmonary hypertension by targeting transforming growth factor beta1. PG - 148-157.e1 LID - S1933-1711(16)30606-4 [pii] LID - 10.1016/j.jash.2016.12.007 [doi] AB - Pulmonary arterial smooth muscle cells (PASMCs) in the medial layer of the vessel wall are involved in vessel homeostasis, but also for pathologic vascular remodeling in diverse diseases, such as pulmonary arterial hypertension (PAH). Pulmonary vascular remodeling in PAH results in vascular disorders, but its underlying molecular mechanisms are still not to be fully disclosed. In this study, we investigated the expression and function of the transforming growth factor (TGF)-beta1 in human PASMC cultured under the condition of hypoxia and elucidated the effect of schisandra chinensis and its active ingredients on proliferation, migration, and apoptosis in human PASMCs. We demonstrated that schisandrin B (Sch.B) alleviated the severity of PAH in PASMCs cultured under the condition of hypoxia. Significant upregulation of TGF-beta1 was observed in hypoxia-induced human PASMCs. Interestingly, administration of Sch.B substantially attenuated TGF-beta1 level in these PASMCs. In order to elucidate Sch.B function, the hypoxia-induced human PASMC was stimulated with Sch.B or cotreatment with TGF-beta1 in vitro. In agreement with its TGF-beta1-reducing effect, Sch B relieved human PASMCs migration and promoted the apoptosis of human PASMCs, by activation of TGF-beta1 downstream signal pathways in PASMCs. In contrast, co-treatment with TGF-beta1 promoted human PASMC proliferation and migration and inhibited the apoptosis of human PASMC, which can attenuate the protective role of Sch.B in human PASMC. Taken collectively, these findings suggest that the vascular relaxation evoked by Sch.B was mediated by direct effect on vascular smooth muscle cell via TGF-beta1 downstream signal pathways. CI - Copyright (c) 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved. FAU - Wu, Jianjun AU - Wu J AD - Department of Cardiology, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China. FAU - Jia, Jing AU - Jia J AD - Department of Cardiology, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China. FAU - Liu, Li AU - Liu L AD - Department of Anesthesiology, The Third Hospital of Harbin Medical University, Harbin, Heilongjiang, China; Key Laboratory of Cardiovascular Medicine Research, Harbin, Heilongjiang, China. FAU - Yang, Fan AU - Yang F AD - Department of Pathophysiology, Harbin Medical University, Harbin, China. FAU - Fan, Yuhua AU - Fan Y AD - Department of Pharmacy, Harbin Medical University, Harbin, China. FAU - Zhang, Sen AU - Zhang S AD - Department of Cardiology, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China. FAU - Yan, Dongxia AU - Yan D AD - Department of Cardiology, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China. FAU - Bu, Rui AU - Bu R AD - Department of Cardiology, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China. FAU - Li, Guangnan AU - Li G AD - Department of Cardiology, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China. FAU - Gao, Yanhui AU - Gao Y AD - Department of Cardiology, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China. FAU - Chen, Yanjun AU - Chen Y AD - Department of Cardiology, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China. Electronic address: chenyanjunhyd@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20161228 PL - United States TA - J Am Soc Hypertens JT - Journal of the American Society of Hypertension : JASH JID - 101312518 RN - 0 (Antineoplastic Agents) RN - 0 (Cyclooctanes) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Lignans) RN - 0 (Polycyclic Compounds) RN - 0 (TGFB1 protein, human) RN - 0 (Transforming Growth Factor beta1) RN - 02XA4X3KZW (schizandrin B) SB - IM MH - Antineoplastic Agents/*pharmacology/therapeutic use MH - Apoptosis/drug effects MH - Cell Movement/drug effects MH - Cells, Cultured MH - Cyclooctanes/pharmacology/therapeutic use MH - Dose-Response Relationship, Drug MH - Drugs, Chinese Herbal MH - Humans MH - Hypertension, Pulmonary/*drug therapy/pathology MH - Hypoxia/complications/pathology MH - Immunochemistry MH - Lignans/*pharmacology/therapeutic use MH - Medicine, Chinese Traditional/methods MH - Muscle, Smooth, Vascular MH - Myocytes, Smooth Muscle MH - Polycyclic Compounds/*pharmacology/therapeutic use MH - Pulmonary Artery/cytology MH - Schisandra/chemistry MH - Signal Transduction/drug effects MH - Transforming Growth Factor beta1/*metabolism MH - Up-Regulation MH - Vascular Remodeling/*drug effects OTO - NOTNLM OT - Apoptosis OT - proliferation OT - pulmonary arterial hypertension OT - schisandra chinensis EDAT- 2017/01/25 06:00 MHDA- 2018/02/23 06:00 CRDT- 2017/01/25 06:00 PHST- 2016/06/20 00:00 [received] PHST- 2016/12/09 00:00 [revised] PHST- 2016/12/18 00:00 [accepted] PHST- 2017/01/25 06:00 [pubmed] PHST- 2018/02/23 06:00 [medline] PHST- 2017/01/25 06:00 [entrez] AID - S1933-1711(16)30606-4 [pii] AID - 10.1016/j.jash.2016.12.007 [doi] PST - ppublish SO - J Am Soc Hypertens. 2017 Mar;11(3):148-157.e1. doi: 10.1016/j.jash.2016.12.007. Epub 2016 Dec 28.