title: Rapamycin attenuates endothelial apoptosis induced by low shear stress via mTOR and sestrin1 related redox regulation.
abstract: BACKGROUND
  Studies indicate the dramatic reduction of shear stress (SS) within the rapamycin eluting stent (RES) segment of coronary arteries. It remains unclear about the role of rapamycin in endothelialization of stented arteries where SS becomes low. Since mTOR (mammalian target of rapamycin) pathway is involved in the antioxidative sestrins expression, we hypothesized that rapamycin attenuated low SS (LSS) induced endothelial dysfunction through mTOR and sestrin1 associated redox regulation.
  
  
  RESULTS
  To mimic the effect of LSS on the stented arteries, a parallel plate flow chamber was used to observe the interplay of LSS and rapamycin on endothelial cells (ECs). The results showed LSS significantly induced EC apoptosis which was mitigated by pretreatment of rapamycin. Rapamycin attenuated LSS induced reactive oxygen species (ROS) and reactive nitrogen species (RNS) production via prohibition of sestrin1 downregulation. Activities of mTORC1 and mTORC2 were detected contradictorily modulated by LSS. Inhibition of rictor expression by target small interfering RNA (siRNA) transfection prohibited sestrin1 downregulation induced by LSS, but inhibition of raptor did not.
  
  
  CONCLUSIONS
  Rapamycin may prohibit sestrin1 downregulation through targeting mTORC2 in appeasing LSS induced EC oxidative apoptosis. Our results provide the in vitro evidence to explain the pathophysiology of RES stented arteries.
authors.affiliation: Department of Cardiology, Nanjing First Hospital Affiliated to Nanjing Medical University, Changle Road 68, Nanjing, Jiangsu 210006, China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Nanjing First Hospital Affiliated to Nanjing Medical University, Changle Road 68, Nanjing, Jiangsu 210006, China.
authors.forename: Zhimei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Nanjing First Hospital Affiliated to Nanjing Medical University, Changle Road 68, Nanjing, Jiangsu 210006, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Nanjing First Hospital Affiliated to Nanjing Medical University, Changle Road 68, Nanjing, Jiangsu 210006, China.
authors.forename: Guangfeng
authors.initials: G
authors.lastname: Zuo
authors.affiliation: Department of Cardiology, Nanjing First Hospital Affiliated to Nanjing Medical University, Changle Road 68, Nanjing, Jiangsu 210006, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Cardiology, Nanjing First Hospital Affiliated to Nanjing Medical University, Changle Road 68, Nanjing, Jiangsu 210006, China.
authors.forename: Wenxing
authors.initials: W
authors.lastname: Mao
authors.affiliation: Department of Cardiology, Nanjing First Hospital Affiliated to Nanjing Medical University, Changle Road 68, Nanjing, Jiangsu 210006, China.
authors.forename: Shaoliang
authors.initials: S
authors.lastname: Chen
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D001158:Arteries / Q000473:pathology; D015536:Down-Regulation; D042783:Endothelial Cells / Q000166:cytology; D004727:Endothelium / Q000473:pathology*; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D033081:Shear Strength; D020123:Sirolimus / Q000494:pharmacology*; D013314:Stress, Mechanical; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D000084622:Sestrins
chemical_list: D000975:Antioxidants; D006360:Heat-Shock Proteins; D007166:Immunosuppressive Agents; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes; D010100:Oxygen; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; C117338:SESN1 protein, human; D000084622:Sestrins