title: Rapamycin promoted thrombosis and platelet adhesion to endothelial cells by inducing membrane remodeling.
abstract: BACKGROUND
  Recently, evidence indicated that the rapamycin-eluting stent which was used worldwide may contribute to an increased risk for thrombosis. On the contrary, other researchers found it was safe. Thus, it is necessary to clarify the effect of rapamycin on thrombosis and the corresponding mechanisms.
  
  
  RESULTS
  The effects of rapamycin in vivo were evaluated by modified deep vein thrombosis animal model. The platelets were from healthy volunteers and the platelet-endothelium (purchased from ATCC) adhesion in cultured endothelial cells was assessed. Membrane rufflings in endothelial cells were examined by confocal and electron microscope. Thrombus formation increased in rats that were injected with rapamycin. Electron microscope analysis exhibited microvilli on the rapamycin-treated endothelium in rats. Rapamycin enhanced membrane ruffling in human umbilical vein endothelial cells (HUVECs) and adhesion of platelets to HUVECs. The platelet-HUVECs adhesion was attenuated when cells were treated with cytochalacin B. Inhibition of autophagy by 3-methyladenine led to suppression of membrane ruffles in HUVECs and augmentation of platelet-endothelial adhesion.
  
  
  CONCLUSIONS
  In conclusion, we found that endothelial membrane remodeling induced by rapamycin is crucial for the adhesion of platelets to endothelial cells and thereby for thrombosis in vivo, and that the endothelial membrane remodeling is autophagy dependent.
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, No,1, DaHua Road, Dong Dan, Beijing 100730, P,R,China. pingjiang@bjmu.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Jiang
authors.forename: Yong
authors.initials: Y
authors.lastname: Lan
authors.forename: Jun
authors.initials: J
authors.lastname: Luo
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Ren
authors.forename: Dong-Ge
authors.initials: DG
authors.lastname: Liu
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Pang
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Cai
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D003571:Cytochalasin B / Q000494:pharmacology; D004195:Disease Models, Animal; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020123:Sirolimus / Q000494:pharmacology* / Q000627:therapeutic use; D013927:Thrombosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
chemical_list: D003571:Cytochalasin B; C025946:3-methyladenine; D000225:Adenine; D020123:Sirolimus