title: Globular adiponectin protects human umbilical vein endothelial cells against apoptosis through adiponectin receptor 1/adenosine monophosphate-activated protein kinase pathway.
abstract: BACKGROUND
  Endothelial dysfunction is a key event in the onset and progression of atherosclerosis in diabetic patients. Apoptosis may lead to endothelial dysfunction and contribute to vascular complications. However, no study has addressed apoptosis in human umbilical vein endothelial cells (HUVECs) induced by an intermittent high-glucose media and its association with adiponectin receptor 1 (adipoR1), adipoR2, or adenosine monophosphate (AMP)-activated protein kinase (AMPK).
  
  
  METHODS
  HUVECs were cultured in continuous normal glucose (5.5 mmol/L), continuous high glucose (25 mmol/L), alternating normal and high glucose and mannitol. In the alternating normal and high-glucose media, HUVECs were treated under different conditions. First, cells were transfected with the adipoR1-specific small-interfering RNA (siRNA) and then stimulated with globular adiponectin (gAD). Second, cells were cultured in both gAD and the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR). Third, cells were cultured in the AMPK inhibitor adenine-9-β-D-arabino-furanoside (araA), gAD, and in AICAR.
  
  
  RESULTS
  HUVEC apoptosis increased more significantly in an intermittent high-glucose medium than in a constant high-glucose medium. HUVEC apoptosis induced by an intermittent high-glucose medium was inhibited when the cells were pretreated with 3 µg/ml gAD, which rapidly activated AMPK and adipoR1 in HUVECs. However, adipoR2 was not activated.
  
  
  CONCLUSIONS
  We found that adipoR1, not adipoR2, is involved in mediating intermittent high-concentration glucose-evoked apoptosis in endothelial cells. gAD activated AMPK through adipoR1, leads to the partial inhibition of HUVEC apoptosis. A fluctuating glucose medium is more harmful than a constant high-glucose medium to endothelial cells.
authors.affiliation: Department of Emergency, Shengjing Hospital, China Medical University, Shenyang, Liaoning 110004, China.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Zhao
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.forename: Tong-Ning
authors.initials: TN
authors.lastname: Yi
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D052242:Adiponectin / Q000494:pharmacology*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D034741:RNA, Small Interfering; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism*; D012265:Ribonucleotides / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: C475418:ADIPOR1 protein, human; D052242:Adiponectin; D034741:RNA, Small Interfering; D054419:Receptors, Adiponectin; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D005947:Glucose