title: High glucose and interleukin 1β-induced apoptosis in human umbilical vein endothelial cells involves in down-regulation of monocarboxylate transporter 4.
abstract: Hyperglycaemia and inflammatory can induce apoptosis in vascular endothelial cells, which contributes to the development of vascular complications in diabetes. Endothelial cells depend on glycolysis for their energy metabolism, and monocarboxylate transporters (MCTs) regulate intracellular pH by mediating the influx and efflux of lactate. Here, we evaluate the role of MCT4 in high glucose (HG) and interleukin 1β (IL-1β)-induced apoptosis in human umbilical vein endothelial cells (HUVECs). We demonstrate that aortic endothelium damage is severe in db/db mice by using scanning ion conductance microscopy (SICM). HG and IL-1β decrease MCT4 and its location on plasma membrane, as well as increase lactic acid accumulation and apoptosis in HUVECs. Knockdown of MCT4 blocks lactate efflux to result in lactic acid accumulation and pH dropping, which is involved in triggering apoptosis in HUVECs.
authors.affiliation: Department of Cardiology, Zhongda Hospital of Southeast University Medical School, Dingjiaqiao Road, 210009, Nanjing, Jiangsu, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Zhongda Hospital of Southeast University Medical School, Dingjiaqiao Road, 210009, Nanjing, Jiangsu, China.
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Zhongda Hospital of Southeast University Medical School, Dingjiaqiao Road, 210009, Nanjing, Jiangsu, China.
authors.forename: Gaoliang
authors.initials: G
authors.lastname: Yan
authors.affiliation: Department of Cardiology, Zhongda Hospital of Southeast University Medical School, Dingjiaqiao Road, 210009, Nanjing, Jiangsu, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: Department of Cardiology, Changzhou Hospital of Nanjing Medical University, Gehu Road, 213004, Changzhou, Jiangsu, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Cardiology, Zhongda Hospital of Southeast University Medical School, Dingjiaqiao Road, 210009, Nanjing, Jiangsu, China.
authors.forename: Boqian
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, Zhongda Hospital of Southeast University Medical School, Dingjiaqiao Road, 210009, Nanjing, Jiangsu, China. Electronic address: tangchengchun@medmail.com.cn.
authors.forename: Chengchun
authors.initials: C
authors.lastname: Tang
authors.affiliation: Institute of Molecular Medicine, Peking University, Yiheyuan Road, 100871, Beijing, China. Electronic address: ycgu@pku.edu.cn.
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D003925:Diabetic Angiopathies / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053583:Interleukin-1beta / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D027501:Monocarboxylic Acid Transporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin / Q000235:genetics
chemical_list: D053583:Interleukin-1beta; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D012333:RNA, Messenger; D054411:Receptors, Leptin; C406962:SLC16A4 protein, human; C515447:leptin receptor, mouse; D019344:Lactic Acid; D005947:Glucose
keywords: Endothelial cells; Endothelium damage; Lactate; Monocarboxylate transporter 4; Scanning ion conductance microscopy