PMID- 30890956 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1664-042X (Print) IS - 1664-042X (Electronic) IS - 1664-042X (Linking) VI - 10 DP - 2019 TI - Ganoderma triterpenes Protect Against Hyperhomocysteinemia Induced Endothelial-Mesenchymal Transition via TGF-beta Signaling Inhibition. PG - 192 LID - 10.3389/fphys.2019.00192 [doi] LID - 192 AB - Endothelial dysfunction is one of the most important pathological status in hyperhomocysteinemia (HHcy) related cardiovascular diseases. Whereas, the underlying mechanisms have not been fully elucidated yet, concomitant with the absence of effective treatment. The purpose of this study was to explore the main mechanisms involved in HHcy-induced endothelial injury and identify the protective effect of Ganoderma triterpenes (GT). Bovine aortic endothelial cells (BAECs) were applied as in vitro experimental model. The small molecular inhibitors were used to explore the signalings involved in HHcy-induced endothelial injury. The experimental results provided initial evidence that HHcy led to endothelial-mesenchymal transition (EndMT). Meanwhile, TGF-beta/Smad, PI3K/AKT and MAPK pathways were activated in this process, which was demonstrated by pretreatment with TGF-beta RI kinase inhibitor VI SB431542, PI3K inhibitor LY294002, p38 inhibitor SB203580, and ERK inhibitor PD98059. Furthermore, it was found that GT restrained the process of HHcy-induced EndMT via reducing oxidative stress and suppressing fore mentioned pathways with further inhibiting the activity of Snail. These results implicate that there is an untapped potential for GT as a novel therapeutic candidate for HHcy-induced EndMT through alleviating oxidative stress and canonical TGF-beta/Smad and non-Smad dependent signaling pathways. FAU - He, Jinzhao AU - He J AD - Key Laboratory of Molecular Cardiovascular Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, China. FAU - Sun, Yi AU - Sun Y AD - Key Laboratory of Molecular Cardiovascular Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, China. FAU - Jia, Yingli AU - Jia Y AD - Key Laboratory of Molecular Cardiovascular Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, China. FAU - Geng, Xiaoqiang AU - Geng X AD - Key Laboratory of Molecular Cardiovascular Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, China. FAU - Chen, Ruoyun AU - Chen R AD - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Chinese Academy of Medical Sciences, Institute of Materia Medica, Peking Union Medical College, Beijing, China. FAU - Zhou, Hong AU - Zhou H AD - Key Laboratory of Molecular Cardiovascular Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, China. FAU - Yang, Baoxue AU - Yang B AD - Key Laboratory of Molecular Cardiovascular Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, China. LA - eng PT - Journal Article DEP - 20190305 PL - Switzerland TA - Front Physiol JT - Frontiers in physiology JID - 101549006 PMC - PMC6412081 OTO - NOTNLM OT - Ganoderma triterpenes OT - TGF-beta OT - endothelial cells OT - endothelial-mesenchymal transition OT - homocysteine OT - oxidative stress EDAT- 2019/03/21 06:00 MHDA- 2019/03/21 06:01 PMCR- 2019/03/05 CRDT- 2019/03/21 06:00 PHST- 2018/10/29 00:00 [received] PHST- 2019/02/15 00:00 [accepted] PHST- 2019/03/21 06:00 [entrez] PHST- 2019/03/21 06:00 [pubmed] PHST- 2019/03/21 06:01 [medline] PHST- 2019/03/05 00:00 [pmc-release] AID - 10.3389/fphys.2019.00192 [doi] PST - epublish SO - Front Physiol. 2019 Mar 5;10:192. doi: 10.3389/fphys.2019.00192. eCollection 2019.