PMID- 32390845 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 11 DP - 2020 TI - Ginsenoside Rg3 Alleviates ox-LDL Induced Endothelial Dysfunction and Prevents Atherosclerosis in ApoE(-/-) Mice by Regulating PPARgamma/FAK Signaling Pathway. PG - 500 LID - 10.3389/fphar.2020.00500 [doi] LID - 500 AB - The initiation of atherosclerosis (AS) induced by dyslipidemia is accompanied by endothelial dysfunction, including decreased healing ability and increased recruitment of monocytes. Studies showed ginsenoside Rg3 has potential to treat diseases associated with endothelial dysfunction which can protects against antineoplastic drugs induced cardiotoxicity by repairing endothelial function, while the effect and mechanism of Rg3 on dyslipidemia induced endothelial dysfunction and AS are not clear. Therefore, we investigated the effects of Rg3 on oxidized low-density lipoprotein (ox-LDL) induced human umbilical vein endothelial cells (HUVECs) dysfunction and high-fat diets (HFD) induced atherosclerosis in ApoE(-/-) mice, as well as the mechanism. For in vitro assay, Rg3 enhanced healing of HUVECs and inhibited human monocytes (THP-1) adhesion to HUVECs disturbed by ox-LDL, down-regulated focal adhesion kinase (FAK)-mediated expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1); restrained the FAK-mediated non-adherent dependent pathway containing matrix metalloproteinase (MMP)-2/9 expression, activation of nuclear factor-kappa B (NF-kappaB), high mRNA levels of monocyte chemotactic protein 1 (MCP-1) and interleukin 6 (IL-6), besides Rg3 up-regulated peroxisome proliferators-activated receptor gamma (PPARgamma) in ox-LDL-stimulated HUVECs. GW9662, the PPARgamma-specific inhibitor, can repressed the effects of Rg3 on ox-LDL-stimulated HUVECs. For in vivo assay, Rg3 significantly reduced atherosclerotic pathological changes in ApoE(-/-) mice fed with HFD, up-regulated PPARgamma, and inhibited activation FAK in aorta, thus inhibited expression of VCAM-1, ICAM-1 in intima. We conclude that Rg3 may protect endothelial cells and inhibit atherosclerosis by up-regulating PPARgamma via repressing FAK-mediated pathways, indicating that Rg3 have good potential in preventing dyslipidemia induced atherosclerosis. CI - Copyright (c) 2020 Geng, Fu, Yu, Lu, Liu, Sun, Yu, Li, Fu, Xu and Sui. FAU - Geng, Jianan AU - Geng J AD - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun, China. FAU - Fu, Wenwen AU - Fu W AD - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun, China. FAU - Yu, Xiaofeng AU - Yu X AD - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun, China. FAU - Lu, Zeyuan AU - Lu Z AD - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun, China. FAU - Liu, Yanzhe AU - Liu Y AD - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun, China. FAU - Sun, Mingyang AU - Sun M AD - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun, China. FAU - Yu, Ping AU - Yu P AD - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun, China. FAU - Li, Xin AU - Li X AD - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun, China. FAU - Fu, Li AU - Fu L AD - Institute of Traditional Chinese Medicine Innovation, Jilin Yatai Pharmaceutical Co., Ltd., Changchun, China. AD - Institute of Dalian Fusheng Natural Medicine, Dalian Fusheng Pharmaceutical Co., Ltd., Dalian, China. FAU - Xu, Huali AU - Xu H AD - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun, China. FAU - Sui, Dayun AU - Sui D AD - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun, China. LA - eng PT - Journal Article DEP - 20200422 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC7188907 OTO - NOTNLM OT - ApoE-/- mice OT - atherosclerosis OT - focal adhesion kinase OT - ginsenoside Rg3 OT - monocyte adhesion OT - peroxisome proliferators-activated receptor gamma EDAT- 2020/05/12 06:00 MHDA- 2020/05/12 06:01 PMCR- 2020/04/22 CRDT- 2020/05/12 06:00 PHST- 2019/08/26 00:00 [received] PHST- 2020/03/30 00:00 [accepted] PHST- 2020/05/12 06:00 [entrez] PHST- 2020/05/12 06:00 [pubmed] PHST- 2020/05/12 06:01 [medline] PHST- 2020/04/22 00:00 [pmc-release] AID - 10.3389/fphar.2020.00500 [doi] PST - epublish SO - Front Pharmacol. 2020 Apr 22;11:500. doi: 10.3389/fphar.2020.00500. eCollection 2020.