PMID- 31811853 OWN - NLM STAT- MEDLINE DCOM- 20200123 LR - 20200123 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 241 DP - 2020 Jan 15 TI - Glibenclamide ameliorates transplant-induced arteriosclerosis and inhibits macrophage migration and MCP-1 expression. PG - 117141 LID - S0024-3205(19)31069-0 [pii] LID - 10.1016/j.lfs.2019.117141 [doi] AB - AIMS: Glibenclamide, a diabetes mellitus type 2 medication, has anti-inflammatory and autoimmune properties. This study investigated the effects of glibenclamide on transplant-induced arteriosclerosis as well as the underlying molecular events. METHODS: Male C57Bl/6 (H-2b) and BALB/c (H-2d) mice were used for aorta transplantation. We used hematoxylin and eosin (HE) and Elastic Van Gieson (EVG) staining for histological assessment, and qRT-PCR and ELISA to measure mRNA and protein levels. Mouse peritoneal macrophages were isolated for lipopolysaccharide (LPS) stimulation and glibenclamide treatment followed by ELISA, Western blot, and Transwell assays. RESULTS: Glibenclamide inhibited transplant-induced arteriosclerosis in vivo. Morphologically, glibenclamide reduced inflammatory cell accumulation and collagen deposition in the aortas. At the gene level, glibenclamide suppressed aortic cytokine mRNA levels, including interleukin-1beta (IL-1beta; 10.64 +/- 3.19 vs. 23.77 +/- 5.72; P < .05), tumor necrosis factor-alpha (TNF-alpha; 4.59 +/- 0.78 vs. 13.89 +/- 5.42; P < .05), and monocyte chemoattractant protein-1 (MCP-1; 202.66 +/- 23.44 vs. 1172.73 +/- 208.80; P < .01), while IL-1beta, TNF-alpha, and MCP-1 levels were also reduced in the mouse sera two weeks after glibenclamide treatment (IL-1beta, 39.40 +/- 13.56 ng/ml vs. 78.96 +/- 9.39 ng/ml; P < .01; TNF-alpha, 52.60 +/- 13.00 ng/ml vs. 159.73 +/- 6.76 ng/ml; P < .01; and MCP-1, 56.60 +/- 9.07 ng/ml vs. 223.07 +/- 36.28 ng/ml; P < .001). Furthermore, glibenclamide inhibited macrophage expression and secretion of inflammatory factors in vitro through suppressing activation of the nuclear factor-kappaB (NF-kappaB) pathway and MCP-1 production. CONCLUSION: Glibenclamide protected against aorta transplantation-induced arteriosclerosis by reducing inflammatory factors in vivo and inhibited macrophage migration and MCP-1 production in vitro. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Zou, Yanqiang AU - Zou Y AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. FAU - Zhou, Cheng AU - Zhou C AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. FAU - Xu, Heng AU - Xu H AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. FAU - Yu, Jizhang AU - Yu J AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. FAU - Ye, Ping AU - Ye P AD - Department of Cardiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan Hubei 430022, China. FAU - Zhang, Hao AU - Zhang H AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. FAU - Chen, Shanshan AU - Chen S AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. FAU - Zhao, Jing AU - Zhao J AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. FAU - Le, Sheng AU - Le S AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. FAU - Cui, Jikai AU - Cui J AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. FAU - Jiang, Lang AU - Jiang L AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. FAU - Wu, Jie AU - Wu J AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. Electronic address: wujie426@hust.edu.cn. FAU - Xia, Jiahong AU - Xia J AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. Electronic address: jiahong.xia@mail.hust.edu.cn. LA - eng PT - Journal Article DEP - 20191204 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Hypoglycemic Agents) RN - SX6K58TVWC (Glyburide) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Arteriosclerosis/*drug therapy/etiology/metabolism/pathology MH - Cell Movement/*drug effects MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Chemokine CCL2/*antagonists & inhibitors/genetics/metabolism MH - Female MH - Gene Expression Regulation/*drug effects MH - Glyburide/*pharmacology MH - Hypoglycemic Agents/pharmacology MH - Macrophages, Peritoneal/*drug effects MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Organ Transplantation/*adverse effects OTO - NOTNLM OT - Glibenclamide OT - MCP-1 OT - Mouse model of graft arteriosclerosis OT - NF-kappaB EDAT- 2019/12/08 06:00 MHDA- 2020/01/24 06:00 CRDT- 2019/12/08 06:00 PHST- 2019/09/12 00:00 [received] PHST- 2019/11/20 00:00 [revised] PHST- 2019/12/01 00:00 [accepted] PHST- 2019/12/08 06:00 [pubmed] PHST- 2020/01/24 06:00 [medline] PHST- 2019/12/08 06:00 [entrez] AID - S0024-3205(19)31069-0 [pii] AID - 10.1016/j.lfs.2019.117141 [doi] PST - ppublish SO - Life Sci. 2020 Jan 15;241:117141. doi: 10.1016/j.lfs.2019.117141. Epub 2019 Dec 4.