title: Enhanced Store-Operated Calcium Entry in Platelets is Associated with Peripheral Artery Disease in Type 2 Diabetes.
abstract: OBJECTIVE
  Platelet dysfunction plays an important role in thrombosis in diabetes with peripheral artery disease (PAD). Store-operated calcium entry (SOCE) and stromal interaction molecule 1 (STIM1) regulate platelet activity by modulating calcium influx. We hypothesized that enhanced SOCE in platelets is associated with diabetes with PAD.
  
  
  METHODS
  We studied the activity of platelets from healthy participants and from type 2 diabetic patients. Platelet calcium influx and protein expression of STIM1 and sarcoendoplasmic reticulum Ca2+-ATPase 3 (SERCA3) were investigated.
  
  
  RESULTS
  Compared with platelets from diabetic patients without PAD, platelets from diabetic patients with PAD exhibited significantly increased SOCE . Menthol administration completely inhibited calcium influx in platelets from diabetic patients without PAD, but this effect was blunted in those from diabetic patients with PAD. Furthermore, the increase in SOCE was correlated with the ankle brachial index (ABI) in diabetic patients. High glucose significantly up-regulated STIM1 and SERCA3 protein expression and induced the phosphorylation of phospholipase C (PLC) in platelets from healthy participants. This effect was attenuated in the presence of menthol or U73122, an inhibitor of PLC. Similarly, significant increases in STIM1 and SERCA3 protein expression were found in platelets from diabetic patients compared to those from healthy participants.
  
  
  CONCLUSIONS
  Platelets from diabetic patients with PAD exhibited enhanced Store-operated calcium influx, which was associated with elevated STIM1/SERCA3 expression via a PLC-dependent pathway and was inhibited by menthol.
authors.forename: Weijie
authors.initials: W
authors.lastname: Xia
authors.forename: Yingsha
authors.initials: Y
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Wang
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Sun
authors.forename: Fang
authors.initials: F
authors.lastname: Sun
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Li
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D000368:Aged; D055109:Ankle Brachial Index; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000175:diagnosis*; D004963:Estrenes / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008610:Menthol / Q000494:pharmacology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D058729:Peripheral Arterial Disease / Q000150:complications / Q000175:diagnosis*; D010766:Phosphorylation / Q000187:drug effects; D011760:Pyrrolidinones / Q000494:pharmacology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D000071737:Stromal Interaction Molecule 1; D019284:Thapsigargin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D004963:Estrenes; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011760:Pyrrolidinones; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D008610:Menthol; D019284:Thapsigargin; D010738:Type C Phospholipases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium